Devices, systems, and methods for treating aneurysms

ABSTRACT

Occlusive devices and associated methods of manufacturing are disclosed herein. Manufacturing an occlusive device can include conforming a mesh to a forming assembly and setting a shape of the mesh based on the forming assembly. In some embodiments, the forming assembly comprises multiple forming members, a mandrel, and/or one or more coupling elements. The method may include everting the mesh over the forming assembly such that the mesh encloses an open volume with a shape based, at least in part, on the shape of the forming assembly. According to some embodiments, setting a shape of the mesh comprises heat-treating the mesh and forming assembly.

CROSS-REFERENCE TO RELATED APPLICATION(S)

The present application claims the benefit of priority of U.S.Provisional Application No. 62/930,421, filed Nov. 4, 2019, U.S.Provisional Application No. 62/930,487, filed Nov. 4, 2019, U.S.Provisional Application No. 62/930,303, filed Nov. 4, 2019, U.S.Provisional Application No. 62/930,324, filed Nov. 4, 2019, U.S.Provisional Application No. 62/930,333, filed Nov. 4, 2019, and U.S.Provisional Application No. 62/930,357, filed Nov. 4, 2019, each ofwhich is incorporated by reference herein in its entirety.

The following applications are also incorporated by reference herein intheir entireties: U.S. patent application Ser. No. ______, filedconcurrently herewith, and titled DEVICES, SYSTEMS, AND METHODS FORTREATMENT OF INTRACRANIAL ANEURYSMS [Attorney Docket No.C00016119.US07]; U.S. patent application Ser. No. ______, filedconcurrently herewith, and titled SYSTEMS AND METHODS FOR TREATINGANEURYSMS [Attorney Docket No. C00016119.US08]; U.S. patent applicationSer. No. ______, filed concurrently herewith, and titled SYSTEMS ANDMETHODS FOR TREATING ANEURYSMS [Attorney Docket No. C00016119.US09];U.S. patent application Ser. No. ______, filed concurrently herewith,and titled SYSTEMS AND METHODS FOR TREATING ANEURYSMS [Attorney DocketNo. C00016119.US10]; U.S. patent application Ser. No. ______, filedconcurrently herewith, and titled ANEURYSM TREATMENT DEVICE [AttorneyDocket No. C00016119.US11]; U.S. patent application Ser. No. ______,filed concurrently herewith, and titled ANEURYSM TREATMENT DEVICE[Attorney Docket No. C00016119.US12]; U.S. patent application Ser. No.______, filed concurrently herewith, and titled DEVICES, SYSTEMS, ANDMETHODS FOR TREATING ANEURYSMS [Attorney Docket No. A0004461US01]; U.S.patent application Ser. No. ______, filed concurrently herewith, andtitled SYSTEMS AND METHODS FOR TREATING ANEURYSMS [Attorney Docket No.A0004538US01]; International application Ser. No. ______, filedconcurrently herewith, titled DEVICES, SYSTEMS, AND METHODS FORTREATMENT OF INTRACRANIAL ANEURYSMS [Attorney Docket No. C00016119WO01];International application Ser. No. ______, filed concurrently herewith,titled SYSTEMS AND METHODS FOR TREATING ANEURYSMS [Attorney Docket No.C00016119WO02]; and International application Ser. No. ______, filedconcurrently herewith, titled SYSTEMS AND METHODS FOR TREATING ANEURYSMS[Attorney Docket No. C00016119W003].

TECHNICAL FIELD

The present technology relates to occlusive devices and associatedmethods of manufacturing.

BACKGROUND

An intracranial aneurysm is a portion of an intracranial blood vesselthat bulges outward from the blood vessel's main channel. This conditionoften occurs at a portion of a blood vessel that is abnormally weakbecause of a congenital anomaly, trauma, high blood pressure, or foranother reason. Once an intracranial aneurysm forms, there is asignificant risk that the aneurysm will eventually rupture and cause amedical emergency with a high risk of mortality due to hemorrhaging.When an unruptured intracranial aneurysm is detected or when a patientsurvives an initial rupture of an intracranial aneurysm, vascularsurgery is often indicated. One conventional type of vascular surgeryfor treating an intracranial aneurysm includes using a microcatheter todispose a platinum coil within an interior volume of the aneurysm. Overtime, the presence of the coil should induce formation of a thrombus.Ideally, the aneurysm's neck closes at the site of the thrombus and isreplaced with new endothelial tissue. Blood then bypasses the aneurysm,thereby reducing the risk of aneurysm rupture (or re-rupture) andassociated hemorrhaging. Unfortunately, long-term recanalization (i.e.,restoration of blood flow to the interior volume of the aneurysm) afterthis type of vascular surgery occurs in a number of cases, especiallyfor intracranial aneurysms with relatively wide necks and/or relativelylarge interior volumes.

Another conventional type of vascular surgery for treating anintracranial aneurysm includes deploying a flow diverter within theassociated intracranial blood vessel. The flow diverter is often a meshtube that causes blood to preferentially flow along a main channel ofthe blood vessel while blood within the aneurysm stagnates. The stagnantblood within the aneurysm should eventually form a thrombus that leadsto closure of the aneurysm's neck and to growth of new endothelialtissue, as with the platinum coil treatment. One significant drawback offlow diverters is that it may take weeks or months to form aneurysmalthrombus and significantly longer for the aneurysm neck to be coveredwith endothelial cells for full effect. This delay may be unacceptablewhen risk of aneurysm rupture (or re-rupture) is high. Moreover, flowdiverters typically require antiplatelet therapy to prevent a thrombusfrom forming within the main channel of the blood vessel at the site ofthe flow diverter. Antiplatelet therapy may be contraindicated shortlyafter an initial aneurysm rupture has occurred because risk ofre-rupture at this time is high and antiplatelet therapy tends toexacerbate intracranial hemorrhaging if re-rupture occurs. For these andother reasons, there is a need for innovation in the treatment ofintracranial aneurysms. Given the severity of this condition, innovationin this field has immediate life-saving potential.

SUMMARY

The present technology is illustrated, for example, according to variousaspects described below. Various examples of aspects of the presenttechnology are described as numbered clauses (1, 2, 3, etc.) forconvenience. These are provided as examples and do not limit the presenttechnology. It is noted that any of the dependent clauses may becombined in any combination, and placed into a respective independentclause, e.g., clause (1, 15, 25, 34, etc.). The other clauses can bepresented in a similar manner.

1. A method for making an occlusive device, the method comprising:

-   -   obtaining a tubular mesh having a lumen therethrough;    -   obtaining a forming member having an outer surface and an inner        surface;    -   everting the mesh over the forming member such that a first        portion of the mesh conforms to the outer surface of the forming        member and a second portion of the mesh conforms to the inner        surface of the forming member;    -   setting a shape of the mesh while positioned over the forming        member.

2. The method of Clause 1, wherein the inner surface of the formingmember is arcuate and defines a cavity in the forming member.

3. The method of Clause 1 or Clause 2, wherein the forming member has asubstantially hemispherical shape.

4. The method of any one of Clauses 1 to 3, wherein the forming memberincludes a lumen extending therethrough.

5. The method of any one of Clauses 1 to 4, wherein the forming memberis a first forming member, the inner surface is a first mating surface,and the method further comprises positioning the second portion of themesh between the first mating surface of the first forming member and asecond mating surface of a second forming member such that the secondportion of the mesh conforms to the first and second mating surfaces ofthe first and second forming members, respectively.

6. The method of Clause 5, further comprising compressing the secondportion of the mesh between the first and second mating surfaces.

7. The method of any one of Clauses 1 to 6, wherein setting the shape ofthe mesh comprises heat-treating the mesh while positioned on theforming member.

8. The method of any one of Clauses 1 to 7, wherein, after setting theshape of the mesh, the first and second portions of the mesh form adual-layer sidewall that encloses an open volume.

9. The method of Clause 8, wherein the dual-layer sidewall has agenerally hollow, hemispherical shape.

10. The method of Clause 8 or Clause 9, wherein the open volume has asubstantially hemispherical shape.

11. The method of Clause 9, wherein the open volume is generally discshaped.

12. The method of any one of Clauses 1 to 11, wherein, after setting theshape of the mesh, the mesh comprises a third portion that is generallytubular.

13. The method of any one of Clauses 8 to 12, further comprisingcoupling a coupling element to the mesh between the third portion of themesh and the first and second portions of the mesh.

14. The method of any one of Clauses 1 to 13, further comprisingpositioning an elongate member within the lumen of the mesh.

15. The method of any one of Clauses 1 to 14, further comprisingpositioning an elongate member within a lumen of the forming member.

16. The method of Clause 14 or Clause 15, wherein the elongate member isa mandrel.

17. The method of any one of Clauses 14 to 16, wherein the elongatemember comprises a generally tubular shape.

18. The method of any one of Clauses 1 to 17, wherein the mesh has aporosity sufficiently low to prevent blood flow across the mesh.

19. The method of any one of Clauses 1 to 18, wherein the mesh comprisesa plurality of braided filaments.

20. The method of any one of Clauses 1 to 19, wherein the mesh comprisesa plurality of interwoven filaments.

21. The method of any one of Clauses 1 to 20, wherein the mesh is alaser-cut tube.

22. The method of any one of Clauses 1 to 21, wherein the mesh comprisesat least two layers.

23. The method of any one of Clauses 1 to Clause 22, wherein the meshcomprises a resilient and/or superelastic material.

24. The method of any one of Clauses 1 to 23, further comprisingcoupling a coupling element to the mesh.

25. The method of Clause 24, wherein the coupling element is coupled tothe mesh such that the coupling element surrounds a circumference of themesh.

26. The method of Clause 24 or Clause 25, wherein the coupling elementcomprises a marker band or wire tie.

27. The method of any one of Clauses 24 to 26, wherein the couplingelement is radiopaque.

28. The method of any one of Clauses 1 to 27, wherein the forming memberhas a substantially cylindrical shape.

29. The method of Clause 28, wherein the forming member defines a lumenextending therethrough.

30. The method of Clause 29, wherein the inner surface is a wall of thelumen.

31. The method of any one of Clauses 1 to 30, wherein, after the shapeof the mesh is set and the mesh is removed from the forming member, themesh comprises a bowl shape with an opening extending through athickness of the bowl.

32. The method of any one of Clauses 1 to 31, wherein, when positionedover the forming member, the first portion of the mesh is spaced apartfrom the second portion of the mesh by a thickness of the forming memberbetween the inner and outer surfaces.

33. A method for making an occlusive device, the method comprising:

-   -   obtaining a tubular mesh having a lumen extending therethrough        and a porosity configured to substantially prevent blood flow        through the mesh, the mesh comprising first and second end        portions and an intermediate portion therebetween;    -   obtaining a forming assembly comprising:        -   a first member having a generally globular shape and a lumen            extending therethrough, wherein the first member has a first            mating surface comprising at least a portion of an outer            surface of the first member; and        -   a second member having a generally hemispherical shape and a            cavity with an arcuate surface, the second member having a            lumen extending therethrough;    -   positioning at least a first portion of the intermediate portion        of the mesh over an outer surface of the second member;    -   positioning at least a portion of the first end portion of the        mesh within the lumen of the first member;    -   positioning at least a second portion of the intermediate        portion of the mesh between the first mating surface of the        first member and the arcuate surface of the second member such        that the second portion substantially conforms to the first        mating surface and the arcuate surface;    -   setting a shape of the mesh while the mesh is positioned on the        forming assembly.

34. The method of Clause 33, further comprising positioning an elongatemember within the lumen of the tubular mesh.

35. The method of Clause 33 or Clause 34, further comprising positioningan elongate member within the lumen of the second member.

36. The method of any one of Clauses 33 to 35, further comprisingpositioning an elongate member within the lumen of the first member.

37. The method of any one of Clauses 34 to 36, further comprisingconforming the first and second end portions of the mesh to an outersurface of the elongate member.

38. The method of any one of Clauses 33 to 37, further comprisingcoupling a coupling element to the second end portion of the mesh at alocation adjacent an outer surface of the second member.

39. The method of any one of Clauses 33 to 38, further comprisingcoupling a coupling element to the first end portion of the mesh at alocation adjacent the arcuate surface of the second member.

40. The method of Clause 38 or Clause 39, wherein the coupling elementsurrounds a circumference of the mesh at the respective first or secondend portion.

41. The method of any one of Clauses 38 to 40, wherein the couplingelement comprises a marker band or wire tie.

42. The method of any one of Clauses 33 to 41, wherein the mesh isself-expanding.

43. The method of any one of Clauses 33 to 42, wherein the tubular meshcomprises a plurality of braided or interwoven filaments.

44. The method of Clause 43, wherein at least some of the filamentscomprise a resilient and/or superelastic material.

45. The method of any one of Clauses 33 to 44, wherein positioning thesecond portion of the intermediate portion of the mesh between the firstmating surface of the first member and the arcuate surface of the secondmember comprises positioning the first member at least partially withinthe cavity of the second member.

46. The method of any one of Clauses 33 to 45, further comprisingcompressing the second portion of the intermediate portion of the meshbetween the first mating surface and the arcuate surface.

47. The method of any one of Clauses 33 to 46, further comprising fixingthe position of the mesh relative to the forming assembly prior tosetting the shape of the mesh.

48. The method of any one of Clauses 33 to 47, wherein setting the shapeof the mesh comprises heat treating the mesh and forming assembly.

49. The method of any one of Clauses 33 to 48, wherein, after settingthe shape of the mesh, the mesh comprises a contoured configuration inwhich the first and second end portions of the mesh have a substantiallytubular shape and the intermediate portion of the mesh is substantiallybowl-shaped.

50. A method for making an occlusive device, the method comprising:

-   -   obtaining a tubular mesh having a lumen extending therethrough        and a porosity configured to substantially prevent blood flow        through the mesh, the mesh comprising first and second end        portions and an intermediate portion therebetween;    -   obtaining a forming member having a first surface, a second        surface opposite the first surface along a thickness of the        forming member, a sidewall therebetween, and a lumen extending        through the first and second surfaces of the forming member;    -   positioning at least a first portion of the intermediate portion        of the mesh within the lumen of the forming member such that the        first end portion of the mesh extends away from the first        surface of the forming member in a first direction and the        second end portion of the mesh extends away from the second        surface of the forming member in a second direction opposite the        first direction;    -   everting the mesh over the forming member such that the first        and second end portions of the mesh extend away from the second        surface of the forming member in the second direction, wherein        everting the mesh causes the first end portion of the mesh to        substantially conform to the first and second surfaces and the        sidewall of the forming member; and    -   setting a shape of the mesh while positioned on the forming        member.

51. The method of Clause 50, further comprising positioning an elongatemember within the lumen of the tubular mesh and the lumen of the formingmember.

52. The method of Clause 51, further comprising conforming the first andsecond end portions of the mesh to an outer surface of the elongatemember.

53. The method of any one of Clauses 50 to 52, wherein the sidewall isannular such that the forming member comprises a generally cylindricalshape.

54. The method of any one of Clauses 50 to 53, further comprisingcoupling a coupling element to the mesh at a location adjacent thesecond surface of the forming member.

55. The method of Clause 54, wherein the coupling element is a markerband or wire tie.

56. The method of any one of Clauses 50 to 53, wherein the tubular meshcomprises a single layer.

57. The method of any one of Clauses 50 to 56, wherein the tubular meshcomprises a plurality of braided or interwoven filaments.

58. The method of Clause 57, wherein at least some of the filamentscomprise a resilient and/or superelastic material.

59. The method of any one of Clauses 50 to 58, wherein setting a shapeof the mesh comprises subjecting the mesh and forming member to a heattreatment procedure.

60. The method of any one of Clauses 50 to 59, wherein, after setting ashape of the mesh, the mesh comprises a contoured configurationcomprising a substantially tubular open end portion, a substantiallytubular intermediate portion, and a substantially disc shaped closed endportion disposed at an angle to the open end and intermediate portions.

61. The method of Clause 60, wherein the forming member is a firstforming member and, after setting the shape of the mesh, the mesh is acontoured mesh, the method further comprising:

-   -   separating the contoured mesh from the first forming member;    -   obtaining a forming assembly comprising a second forming member        and a third forming member, wherein:        -   the second forming member comprises a body portion having a            first surface, a second surface opposite the first surface            along a thickness of the second forming member, a sidewall            therebetween, a protrusion extending from the first surface            in a first direction, and a lumen extending through the body            portion and the protrusion; and        -   the third forming member comprises a body portion having a            first surface, a second surface opposite the first surface            along a thickness of the third forming member, a sidewall            therebetween, and a lumen extending through the body            portion;    -   positioning the intermediate portion of the contoured mesh        within the lumen of the second forming member such that the        closed end portion of the contoured mesh extends from the first        surface of the second forming member and the open end portion of        the contoured mesh extends from the second surface of the second        forming member;    -   positioning the closed end portion of the contoured mesh between        the first surface and the protrusion of the second forming        member and the second surface of the third forming member such        that the closed end portion of the contoured mesh conforms to        the first surface and the protrusion of the second forming        member; and    -   setting a second shape of the contoured mesh based on the second        and third forming members.

62. The method of Clause 61, wherein the protrusion is substantiallycylindrical.

63. The method of Clause 61 or Clause 62, wherein a first portion of thelumen of the second forming member comprises a first diameter and asecond portion of the lumen of the second forming member comprises asecond diameter different than the first diameter.

64. The method of any one of Clauses 61 to 63, further comprisingpositioning an elongate shaft within the lumen of the contoured mesh,the lumen of the second forming member, and the lumen of the thirdforming member.

65. The method of any one of Clauses 61 to 64, further comprisingcoupling a coupling element to the contoured mesh.

66. The method of any one of Clauses 61 to 65, wherein, after setting asecond shape of the contoured mesh, the contoured mesh comprises asubstantially tubular open end portion, a substantially tubularintermediate portion, and a closed end portion disposed at an angle tothe open end and intermediate portions, wherein the closed end portionis substantially disc shaped with a protruding region.

67. The method of Clause 66, wherein the protruding region issubstantially cylindrical.

68. A method for treating an aneurysm, the method comprising:

-   -   positioning a distal end of an elongated shaft in an aneurysm        cavity;    -   releasing an occlusive member from the elongated shaft while the        distal end of the elongated shaft is positioned within the        aneurysm cavity such that the occlusive member self-expands to        assume a first expanded state in which the occlusive member        forms a first shape, wherein, in the first expanded state, the        occlusive member encloses an interior region having a first        interior volume; and    -   delivering an embolic element between the occlusive member and        the aneurysm wall to transform the occlusive member into a        second expanded state in which the occlusive member defines a        second interior volume less than the first interior volume,        wherein the occlusive member forms a second shape in the second        expanded state that is different than the first shape in the        first expanded state.

69. The method of any one of the previous Clauses, wherein transformingthe occlusive member into the second expanded shape includes injectingthe embolic material to urge a portion of a sidewall of the expandablemesh in a direction away from a wall of the aneurysm and towards theinterior region of the occlusive member.

70. The method of any one of the previous Clauses, wherein transformingthe occlusive member into the second expanded shape includes injectingthe embolic material to invert a portion of a sidewall of the occlusivemember such that the portion is convex towards the aneurysm wall in thefirst expanded state and concave towards the aneurysm wall in the secondexpanded state.

71. The method of any one of the previous Clauses, wherein the embolicelement comprises a liquid embolic.

72. The method of any one of the previous Clauses, wherein the embolicelement comprises one or more embolization coils.

73. The method of any one of the previous Clauses, wherein deliveringthe embolic element occurs after the occlusive member is in the firstexpanded state.

74. The method of any one of the preceding Clauses, wherein theocclusive member is a mesh.

75. The method of any one of the preceding Clauses, wherein theocclusive member is a braid.

76. The method of any one of the preceding Clauses, wherein theocclusive member is a dual-layered braid.

77. The method of any one of the preceding Clauses, wherein theocclusive member has a globular or generally spherical shape in thefirst expanded state.

78. The method of any one of the preceding Clauses, wherein theocclusive member is cup or bowl-shaped in the second expanded state.

79. The method of any one of the preceding Clauses, wherein the secondshape is a predetermined three-dimensional shape.

80. The method of any one of the preceding Clauses, wherein theocclusive member forms a multi-layer braid at the neck of the aneurysmin the second expanded state.

81. The method of any one of the previous Clauses, wherein the occlusivemember comprises a plurality of braided filaments that assume a pre-set,three-dimensional shape in the expanded state.

82. The method of any one of the previous Clauses, wherein the occlusivemember comprises a braid formed of 24, 32, 36, 48, 64, or 72 filaments.

83. The method of any one of the previous Clauses, wherein the occlusivemember comprises a braid formed of a plurality of wires, some or all ofwhich have a diameter of about 0.001 inches (0.00254 cm).

84. The method of any one of the previous Clauses, wherein the occlusivemember comprises a braid formed of a plurality of wires, some or all ofwhich have the same diameter.

85. The method of any one of the previous Clauses, wherein the occlusivemember comprises a braid formed of a plurality of wires, at least someof which have different diameters.

86. The method of any one of the previous Clauses, wherein the occlusivemember forms a closed, globular shape in the expanded state, the meshhaving an aperture at a distal portion.

87. The method of any one of the previous Clauses, wherein, in theexpanded state, the occlusive member forms one of a sphere, a prolatespheroid, or an oblate spheroid.

88. The method of any one of the previous Clauses, wherein the occlusivemember comprises an inner layer and an outer layer.

89. The method of any one of the previous Clauses, wherein the occlusivemember comprises an inner layer and an outer layer that meet at a foldat a distal portion of the occlusive member.

90. The method of Clause 22, wherein the expandable mesh includes anaperture at a distal portion, the aperture being defined by the fold.

91. The method of any one of the previous Clauses, wherein the occlusivemember comprises an inner layer and an outer layer that meet at a foldat a proximal portion of the occlusive member.

92. The method of Clause 24, wherein the expandable mesh includes anaperture at a distal portion, the aperture being defined by the fold.

93. The method of any one of the previous Clauses, wherein the occlusivemember has a maximum cross-sectional dimension of 3.0 mm, 3.5 mm, 4.0mm, 4.5 mm, 5.0 mm, 5.5 mm, 6.0 mm, 6.5 mm, 7.0 mm, 7.5 mm, or 8.0 mm.

94. The method of any one of the previous Clauses, wherein the occlusivemember is formed of a plurality of filaments having first and secondends fixed at a coupler.

95. The method of any one of the previous Clauses, wherein the occlusivemember is formed of a plurality of filaments formed of an inner corematerial surrounded by an outer material.

96. The method of Clause 28, wherein the inner core material is aradiopaque material and the outer material is a superelastic material.

97. The method of any one of the previous Clauses, wherein the occlusivemember is a laser-cut tube.

98. The method of any one of the previous Clauses, wherein the occlusivemember comprises a plurality of filaments.

99. The method of Clause 31, wherein the filaments are interwoven.

100. The method of Clause 31 or Clause 32, wherein the filaments arebraided.

101. The method of any one of Clauses 31 to 33, wherein each of thefilaments has a first end and a second end opposite the first end, andwherein both the first and second ends of the filaments are fixedrelative to one another at a coupler.

102. The method of Clause 34, wherein the coupler is disposed at adistal end of the occlusive member.

103. The method of Clause 34, wherein the coupler is disposed at aproximal end of the occlusive member.

104. The method of any one of Clauses 31 to 36, wherein each of thefilaments terminate at only one end of the occlusive member.

105. The method of Clause 37, wherein the filaments form an opening atan end of the occlusive member opposite the only one end.

106. The method of Clause 38, wherein an inverted portion of each of thefilaments define the opening.

107. The method of Clause 39, wherein the inverted portions of thefilaments are configured to move relative to one another.

108. The method of any one of the previous Clauses, wherein the embolicelement comprises a biopolymer and a chemical crosslinking agent.

109. The method of Clause 42, wherein the biopolymer includes chitosan,a derivative of chitosan, an analog of chitosan, or a combinationthereof.

110. The method of Clause 42 or Clause 43, wherein the chemicalcrosslinking agent includes genipin, a derivative of genipin, an analogof genipin, or a combination thereof.

111. The method of any one of Clauses 42 to 44, wherein the embolicelement further comprises a physical crosslinking agent.

112. The method of Clause 45, the physical crosslinking agent includes βglycerophosphate, a derivative of β glycerophosphate, an analog of βglycerophosphate, or a combination thereof.

113. The method of Clause 42, wherein

-   -   the biopolymer includes chitosan, a derivative of chitosan, an        analog of chitosan, or a combination thereof;    -   the chemical crosslinking agent includes genipin, a derivative        of genipin, an analog of genipin, or a combination thereof; and    -   the physical crosslinking agent includes β glycerophosphate, a        derivative of β glycerophosphate, an analog of β        glycerophosphate, or a combination thereof.

114. The method of any one of the preceding Clauses, wherein the embolicelement comprises a contrast agent.

115. The method of Clause 48, wherein the contrast agent is selected toprovide diminishing radiopacity.

116. The method of Clause 48 or Clause 49, wherein the contrast agentincludes iohexol, a derivative of iohexol, an analog of iohexol, or acombination thereof.

117. A method for treating an aneurysm, the method comprising:

-   -   positioning an expandable occlusive member in an initial        expanded state within an aneurysm, wherein in the initial        expanded state the expandable occlusive member provides a number        of layers across a neck of the aneurysm; and    -   doubling the number of layers of the occlusive device across the        neck of the aneurysm by introducing an embolic element to the        aneurysm cavity.

118. The method of Clause 51, wherein the number of layers is one.

119. The method of Clause 51, wherein the number of layers is two.

120. The method of any one of Clauses 51 to 53, wherein the layers aremesh layers.

121. The method of any one of Clauses 51 to 54, wherein the occlusivemember has a first shape in the initial expanded state, and whereinintroducing the embolic element transforms the occlusive member from theinitial expanded state to a secondary expanded state in which theocclusive member forms a second shape different than the first shape.

122. The method of Clause 55, wherein a volume enclosed by the firstshape is greater than a volume enclosed by the second shape.

123. A method for imaging treatment of an aneurysm, the methodcomprising:

-   -   acquiring a first image visualizing:        -   an occlusive member positioned within an aneurysm, the            occlusive member including a first radiopaque marker; and        -   a conduit having a distal portion positioned within an            aneurysm, the distal portion of the conduit including a            second radiopaque marker; and    -   acquiring a second image in which the first radiopaque marker is        further from the second radiopaque marker than in the first        image.

124. The method of Clause 56, wherein, in the second image, the firstradiopaque marker is positioned proximal to the second radiopaquemarker.

125. The method of one of Clauses 56 to 57, wherein, in the secondimage, the first radiopaque marker is positioned closer to a neck of theaneurysm than in the first image.

126. The method of any one of Clauses 56 to 58, wherein, in the firstimage, the first radiopaque marker is positioned in a distal half of theocclusive member.

127. The method of any one of Clauses 56 to 59, wherein, in the firstimage, the first radiopaque marker is positioned on a distal-facingsurface of the occlusive member.

128. The method of any one of Clauses 56 to 60, wherein, in the firstimage, the first radiopaque marker is positioned proximal to the secondradiopaque marker.

129. The method of any one of Clauses 56 to 61, wherein, in the firstimage and in the second image, the second radiopaque marker is disposednearer to a dome of the aneurysm than the first radiopaque marker.

130. The method of any one of Clauses 56 to 62, wherein, in the secondimage, a radiopaque occlusive element is visible in a space between thefirst radiopaque marker and the second radiopaque marker.

131. The method of any one of Clauses 56 to 63, further comprisingacquiring a third image in which the first radiopaque marker is furtherfrom the second radiopaque marker than in the second image.

132. The method of any one of Clauses 56 to 64, wherein acquiring thefirst image and acquiring the second image each comprises acquiring afluoroscopic image.

133. A device for treating an aneurysm, the device comprising:

-   -   a mesh having an expanded, unconstrained state, the mesh formed        of a plurality of braided filaments, each of the filaments        having a first end and a second end, wherein the mesh has a        proximal portion configured to be positioned over the neck of an        aneurysm and a distal portion;    -   a first coupler at the proximal portion, wherein the first ends        are secured relative to one another at the first coupler; and    -   a second coupler at the distal portion, wherein the second ends        are secured relative to one another at the second coupler,    -   wherein the mesh is formed of a wall comprising a first portion,        a second portion, and a ridge, wherein the first portion extends        between the first coupler and the ridge and the second portion        extends between the ridge and the second coupler, and    -   wherein the mesh includes a cavity at the distal portion, and        wherein all or a portion of the distal coupler is positioned        within the cavity.

134. The device of Clause 133, wherein the mesh has a single layerdelivery configuration.

BRIEF DESCRIPTION OF THE DRAWINGS

Many aspects of the present disclosure can be better understood withreference to the following drawings. The components in the drawings arenot necessarily to scale. Instead, emphasis is placed on illustratingclearly the principles of the present disclosure.

FIG. 1A shows a perspective view of a system for treating an aneurysm inaccordance with the present technology.

FIG. 1B shows an enlarged view of a distal portion of the treatmentsystem of FIG. 1A in accordance with the present technology.

FIGS. 1C and 1D are sectioned views of occlusive members in an expandedstate in accordance with the present technology.

FIG. 2 shows an embolic kit according to the present technology.

FIGS. 3A-3G depict an example method of treating an aneurysm with thetreatment systems of the present technology.

FIGS. 4A-5B show various types of images that may be employed to confirmand/or monitor deployment of the treatment system of the presenttechnology.

FIG. 6A is a side view of an occlusive member configured in accordancewith several embodiments of the present technology.

FIGS. 6B and 6C are isometric and cross-sectional views, respectively,of the occlusive member shown in FIG. 6A.

FIGS. 7 and 8 are cross-sectional views of different occlusive membersconfigured in accordance with several embodiments of the presenttechnology.

FIG. 9A is a side view of an occlusive member configured in accordancewith several embodiments of the present technology.

FIG. 9B is a side view of the occlusive member of FIG. 9A shown deployedin a transparent tube.

FIGS. 10A, 10B and 10C are isometric, cross-sectional, and side views,respectively, of an occlusive member configured in accordance withseveral embodiments of the present technology.

FIGS. 11A and 11B are side and cross-sectional views, respectively, ofan occlusive member configured in accordance with several embodiments ofthe present technology.

FIG. 12 is a side view of the occlusive member of FIGS. 11A and 11Bshown deployed in a transparent tube.

FIGS. 13A and 13B are side and cross-sectional views, respectively, ofan occlusive member configured in accordance with several embodiments ofthe present technology.

FIGS. 14A and 14B are side and cross-sectional views, respectively, ofan occlusive member configured in accordance with several embodiments ofthe present technology.

FIGS. 15A and 15B are side and cross-sectional views, respectively, ofan occlusive member configured in accordance with several embodiments ofthe present technology.

FIG. 16 depicts a forming assembly configured in accordance with severalembodiments of the present technology.

FIGS. 17A-17D are cross-sectional views of a forming assembly and a meshat various stages of a method for making an occlusive device inaccordance with several embodiments of the present technology.

FIG. 18A depicts a forming member configured in accordance with severalembodiments of the present technology.

FIG. 18B is a cross-sectional view of the forming member shown in FIG.18A, taken along line 18B-18B.

FIGS. 19A-19C are cross-sectional views of a forming member and a meshat various stages of a method for making an occlusive device inaccordance with several embodiments of the present technology.

FIG. 20A depicts a forming assembly configured in accordance withseveral embodiments of the present technology.

FIG. 20B is a cross-sectional view of the forming assembly shown in FIG.20A, taken along line 20B-20B.

FIGS. 21A-21C are cross-sectional views of a forming assembly and a meshat various stages of a method for making an occlusive device inaccordance with several embodiments of the present technology.

FIG. 21D is a cross-sectional view of a mesh configured in accordancewith several embodiments of the present technology.

DETAILED DESCRIPTION

The

Methods for treating intracranial aneurysms in accordance with at leastsome embodiments of the present technology include positioning anexpandable occlusive member within the aneurysm and introducing anembolic element between the occlusive member and an aneurysm wall.Introduction of the embolic element both fills space within the aneurysmcavity and deforms the occlusive member from a first expanded state to asecond expanded state to fortify the occlusive member at the neck of theaneurysm. Deformation of the occlusive member from a first expandedstate to a second expanded state provides the additional advantage ofgiving visual confirmation to the physician that the delivered amount ofembolic element sufficiently fills the aneurysm cavity. In addition toproviding a structural support and anchor for the embolic element, theocclusive member provides a scaffold for tissue remodeling and divertsblood flow from the aneurysm. Moreover, the embolic element exerts asubstantially uniform pressure on the occlusive member towards the neckof the aneurysm, thereby pressing the portions of the occlusive memberpositioned adjacent the neck against the inner surface of the aneurysmwall such that the occlusive member forms a complete and stable seal atthe neck.

Specific details of systems, devices, and methods for treatingintracranial aneurysms in accordance with embodiments of the presenttechnology are described herein with reference to FIGS. 1A-5B. Althoughthese systems, devices, and methods may be described herein primarily orentirely in the context of treating saccular intracranial aneurysms,other contexts are within the scope of the present technology. Forexample, suitable features of described systems, devices, and methodsfor treating saccular intracranial aneurysms can be implemented in thecontext of treating non-saccular intracranial aneurysms, abdominalaortic aneurysms, thoracic aortic aneurysms, renal artery aneurysms,arteriovenous malformations, tumors (e.g. via occlusion of vessel(s)feeding a tumor), perivascular leaks, varicose veins (e.g. via occlusionof one or more truncal veins such as the great saphenous vein),hemorrhoids, and sealing endoleaks adjacent to artificial heart valves,covered stents, and abdominal aortic aneurysm devices among otherexamples. Furthermore, it should be understood, in general, that othersystems, devices, and methods in addition to those disclosed herein arewithin the scope of the present disclosure. For example, systems,devices, and methods in accordance with embodiments of the presenttechnology can have different and/or additional configurations,components, procedures, etc. than those disclosed herein. Moreover,systems, devices, and methods in accordance with embodiments of thepresent disclosure can be without one or more of the configurations,components, procedures, etc. disclosed herein without deviating from thepresent technology.

I. Overview of Systems of the Present Technology

FIG. 1A illustrates a view of a system 10 for treating intracranialaneurysms according to one or more embodiments of the presenttechnology. As shown in FIG. 1A, the system 10 comprises a treatmentsystem 100 and an embolic kit 200 for use with one or more components ofthe treatment system 100. The treatment system 100 may comprise anocclusive member 102 (shown in an expanded state) detachably coupled toa delivery system, and the delivery system may be configured tointravascularly position the occlusive member 102 within an aneurysm.The embolic kit 200 may comprise one or more substances or devices thatalone or in combination form an embolic element that is configured toco-occupy the internal volume of the aneurysm with the occlusive member102. In some embodiments, the treatment system 100 may be configured todeliver the embolic element (and/or one or more precursors thereof) tothe aneurysm. Additionally or alternatively, the system 10 may include aseparate delivery system (not shown) for delivering the embolic element(and/or one or more precursors thereof) to the aneurysm cavity.

As shown in FIG. 1A, the treatment system 100 has a proximal portion 100a configured to be extracorporeally positioned during treatment and adistal portion 100 b configured to be intravascularly positioned withina blood vessel (such as an intracranial blood vessel) at a treatmentsite at or proximate an aneurysm. The treatment system 100 may include ahandle 103 at the proximal portion 100 a, the occlusive member 102 atthe distal portion 100 b, and a plurality of elongated shafts or membersextending between the proximal and distal portions 100 a and 100 b. Insome embodiments, such as that shown in FIG. 1A, the treatment system100 may include a first elongated shaft 109 (such as a guide catheter orballoon guide catheter), a second elongated shaft 108 (such as amicrocatheter) configured to be slidably disposed within a lumen of thefirst elongated shaft 109, and an elongated member 106 configured to beslidably disposed within a lumen of the second elongated shaft 108. Insome embodiments, the treatment system 100 does not include the firstelongated shaft 109 and only includes the second elongated shaft 108.

FIG. 1B is an enlarged view of the distal portion 100 b of the treatmentsystem 100. Referring to FIGS. 1A and 1B together, the occlusive member102 may be detachably coupled to a distal end of the elongated member106. For example, the elongated member 106 may include a first coupler112 at its distal end, and the occlusive member 102 may include a secondcoupler 114 configured to detachably couple with the first coupler 112.The treatment system 100 may further comprise a conduit 116 extendingfrom the handle 103 (for example, via port 110) distally to the distalportion 100 b of the treatment system 100. The conduit 116 is configuredto deliver the embolic element (and/or one or more precursors thereof)through one or more components of the delivery system (e.g., the firstor second elongated shafts 109, 108, the elongated member 106, etc.) toa position at the exterior of the occlusive member 102. As such, theembolic element may be positioned between the occlusive member 102 andan inner wall of the aneurysm cavity, as described in greater detailbelow.

According to some embodiments, the second elongated shaft 108 isgenerally constructed to track over a conventional guidewire in thecervical anatomy and into the cerebral vessels associated with the brainand may also be chosen according to several standard designs that aregenerally available. Accordingly, the second elongated shaft 108 canhave a length that is at least 125 cm long, and more particularly may bebetween about 125 cm and about 175 cm long. In some embodiments, thesecond elongated shaft 108 may have an inner diameter of about 0.015inches (0.0381 cm), 0.017 inches (0.043 cm), about 0.021 inches (0.053cm), or about 0.027 inches (0.069 cm). Other designs and dimensions arecontemplated.

The elongated member 106 can be movable within the first and/or secondelongated shafts 109, 108 to position the occlusive member 102 at adesired location. The elongated member 106 can be sufficiently flexibleto allow manipulation, e.g., advancement and/or retraction, of theocclusive member 102 through tortuous passages. Tortuous passages caninclude, for example, catheter lumens, microcatheter lumens, bloodvessels, urinary tracts, biliary tracts, and airways. The elongatedmember 106 can be formed of any material and in any dimensions suitablefor the task(s) for which the system is to be employed. In someembodiments, the elongated member 106 can comprise a solid metal wire.In some embodiments, the elongated member 106 may comprise any othersuitable form of shaft such as an elongated tubular shaft.

In some embodiments, the elongated member 106 can comprise stainlesssteel, nitinol, or other metal or alloy. In some embodiments, theelongated member 106 can be surrounded over some or all of its length bya coating, such as, for example, polytetrafluoroethylene. The elongatedmember 106 may have a diameter that is generally constant along itslength, or the elongated member 106 may have a diameter that tapersradially inwardly, along at least a portion of its length, as it extendsin a distal direction.

According to several embodiments, the conduit 116 may be a catheter orelongated shaft that is delivered separately from the second elongatedshaft 108.

A. Selected Examples of Occlusive Members

FIG. 1C is a sectioned view of the occlusive member 102, shown in anexpanded state and detached from the treatment system 100. Referring toFIGS. 1B and 1C, the occlusive member 102 may comprise an expandableelement having a low-profile or constrained state while positionedwithin a catheter (such as the second elongated shaft 108) for deliveryto the aneurysm and an expanded state in which the expandable element isconfigured to be positioned within an aneurysm (such as a cerebralaneurysm).

According to some embodiments, the occlusive member 102 may comprise amesh 101 formed of a plurality of braided filaments that have beenheat-set to assume a predetermined shape enclosing an interior volume130 when the mesh 101 is in an expanded, unconstrained state. Exampleshapes include a globular shape, such as a sphere, a prolate spheroid,an oblate spheroid, and others. As depicted in FIG. 1C, the mesh 101 mayhave inner and outer layers 122, 124 that have proximal ends fixedrelative to one another at the second coupler 114 and meet distally at adistal fold 128 surrounding an aperture 126. While the inner and outerlayers 122, 124 are depicted spaced apart from one another along theirlengths, the inner and outer layers 122, 124 may be in contact with oneanother along all or a portion of their lengths. For example, the innerlayer 122 may press radially outwardly against the outer layer 124. Insome embodiments, the occlusive member 102 may be formed of a singlelayer or mesh or braid.

In some embodiments, the inner and outer layers 122, 124 have theirdistal ends fixed relative to one another at a distal coupler and meetproximally at a proximal fold surrounding an aperture. In any case, insome embodiments the conduit 116 may be configured to be slidablypositioned through some or all of the second coupler 114, the interiorvolume 130 of the expanded mesh 101, and the opening 126.

The inner and outer layers 122 and 124 may conform to one another at thedistal portion (for example as shown in FIG. 1C) to form a curved distalsurface. For example, at least at the distal portion of the occlusivemember 102, the inner and outer layers 122 and 124 may extend distallyand radially inwardly, towards the aperture 126. In some embodiments,the outer and/or inner layers 122 and 124 extend distally and radiallyoutwardly from the second coupler 114, then extend distally and radiallyinwardly up to a distal terminus of the occlusive member 102 (e.g., thefold 128). The occlusive member 102 and/or layers thereof may be curvedalong its entire length, or may have one or more generally straightportions. In some embodiments, the curved surface transitions to a flator substantially flat, distal-most surface that surrounds the aperture126. In some embodiments, the curved surface transitions to adistal-most surface that surrounds the aperture 126 and has a radius ofcurvature that is greater than the average radius of curvature of therest of the occlusive member 102. Having a flat or substantially flatdistal surface, or a distal surface with a radius of curvature that isgreater than the average radius of curvature of the rest of theocclusive member 102, may be beneficial for delivering the embolicelement 230 in that it creates a small gap between the distal surface ofthe occlusive member 102 and the dome of the aneurysm A (see, forexample, FIG. 3B). In some embodiments, the surface of the occlusivemember 102 surrounding the aperture 126 is curved and/or has generallythe same radius of curvature as the remainder of the occlusive member102.

In any case, the inner layer 124 may have a shape that substantiallyconforms to the shape of the outer layer 124, or the inner and outerlayers 122, 124 may have different shapes. For example, as shown in FIG.1D, the inner layer 122 may have a diameter or cross-sectional dimensionthat is less than the outer layer 124. Such a configuration may bebeneficial in that the embolic element 230 experiences less resistance,at least initially, when pushing the distal wall of the occlusive member102 downwardly towards the neck (as described in greater detail below).

In any case, both the proximal portion and the distal portion of themesh 101 can form generally closed surfaces. However, unlike at theproximal portion of the mesh 101, the portion of the filaments at ornear the fold 128 at the distal portion of the mesh 101 can moverelative to one another. As such, the distal portion of the mesh 101 hasboth the properties of a closed end and also some properties of an openend (like a traditional stent), such as some freedom of movement of thedistal-most portions of the filaments and an opening through which theconduit 116, a guidewire, guidetube, or other elongated member may passthrough.

In some embodiments, each of the plurality of filaments have a first endpositioned at the proximal portion of the mesh 101 and a second end alsopositioned at the proximal portion of the mesh 101. Each of thefilaments may extend from its corresponding first end distally along thebody of the mesh 101 to the fold 128, invert, then extend proximallyalong the mesh body to its corresponding second end at the proximalportion of the mesh 101. As such, each of the plurality of filamentshave a first length that forms the inner layer 122 of the mesh 101, asecond length that forms the outer layer 124 of the mesh 101, and bothfirst and second ends fixed at the proximal portion of the mesh 101. Insome embodiments, the occlusive member 102 may comprise a mesh formed ofa single layer, or a mesh formed of three or more layers.

In some embodiments, the distal end surface of the mesh 101 iscompletely closed (i.e., does not include an aperture). In someembodiments the filaments are fixed relative to one another at both theproximal and distal ends of the occlusive member 102.

The mesh 101 may be formed of metal wires, polymer wires, or both, andthe wires may have shape memory and/or superelastic properties. The mesh101 may be formed of 24, 32, 36, 48, 64, 72, 96, 128, or 144 filaments.The mesh 101 may be formed of a range of filament or wire sizes, such aswires having a diameter of from about 0.0004 inches to about 0.0020inches, or of from about 0.0009 inches to about 0.0012 inches. In someembodiments, each of the wires or filaments have a diameter of about0.0004 inches, about 0.0005 inches, about 0.0006 inches, about 0.0007inches, about 0.0008 inches, about 0.0009 inches, about 0.001 inches,about 0.0011 inches, about 0.0012 inches, about 0.0013 inches, about0.0014 inches, about 0.0015 inches, about 0.0016 inches, about 0.0017inches, about 0.0018 inches, about 0.0019 inches, or about 0.0020inches. In some embodiments, all of the filaments of the braided mesh101 may have the same diameter. For example, in some embodiments, all ofthe filaments have a diameter of about 0.001 inches. In someembodiments, some of the filaments may have different cross-sectionaldiameters. For example, some of the filaments may have a slightlythicker diameter to impart additional strength to the braided layers. Insome embodiments, some of the filaments can have a diameter of about0.001 inches, and some of the filaments can have a diameter of greaterthan 0.001 inches. The thicker filaments may impart greater strength tothe braid without significantly increasing the device delivery profile,with the thinner wires offering some strength while filling-out thebraid matrix density.

The occlusive member 102 can have different shapes and sizes in anexpanded, unconstrained state. For example, the occlusive member 102 mayhave a bullet shape, a barrel-shape, an egg shape, a dreidel shape, abowl shape, a disc shape, a cylindrical or substantially cylindricalshape, a barrel shape, a chalice shape, etc.

B. Selected Examples of Embolic Kits

The embolic kit 200 may include one or more precursors for creation of aliquid embolic. For example, the embolic kit 200 may include a firstcontainer 202 containing a first precursor material 203 (shownschematically), a second container 204 containing a second precursormaterial 205 (also shown schematically), and a mixing device 206suitable for mixing the first and second precursor materials 203, 205.The mixing device 206 can include mixing syringes 208 (individuallyidentified as mixing syringes 208 a, 208 b) and a coupler 210 extendingbetween respective exit ports (not shown) of the mixing syringes 208.The mixing syringes 208 a, 208 b each include a plunger 212 and a barrel214 in which the plunger 212 is slidably received.

The embolic kit 200 can further include an injection syringe 216configured to receive a mixture of the first and second precursormaterials 203, 205 and deliver the mixture to a proximal portion 100 bof the treatment assembly 100. The injection syringe 216 can include abarrel 220, an exit port 222 at one end of the barrel 220, and a plunger224 slidably received within the barrel 220 via an opposite end of thebarrel 220. The handle 103 of the treatment system 100 may have acoupler configured to form a secure fluidic connection between the lumenand the exit port 222 of the injection syringe 216.

The first and second precursor materials 203, 205 can include abiopolymer and a chemical crosslinking agent, respectively. The chemicalcrosslinking agent can be selected to form covalent crosslinks betweenchains of the biopolymer. In some embodiments, the biopolymer of thefirst precursor material 203 includes chitosan or a derivative or analogthereof, and the chemical crosslinking agent of the second precursormaterial 205 includes genipin or a derivative or analog thereof. Othersuitable crosslinking agents for use with chitosan includeglutaraldehyde, functionalized polyethylene glycol, and derivatives andanalogs thereof. In other embodiments, the biopolymer of the firstprecursor material 203 can include collagen or a derivative or analogthereof, and the chemical crosslinking agent of the second precursormaterial 205 can include hexamethylene diisocyanate or a derivative oranalog thereof. Alternatively or in addition, genipin or a derivative oranalog thereof can be used as a chemical crosslinking agent for acollagen-based biopolymer. In still other embodiments, the biopolymer ofthe first precursor material 203 and the chemical crosslinking agent ofthe second precursor material 205 can include other suitable compoundsalone or in combination.

Mixing the biopolymer of the first precursor material 203 and thechemical crosslinking agent of the second precursor material 205 caninitiate chemical crosslinking of the biopolymer. After the first andsecond precursor materials 203, 205 are mixed, chemical crosslinking ofthe biopolymer occurs for enough time to allow the resulting embolicelement 230 be delivered to the aneurysm before becoming too viscous tomove through the lumen of the conduit 116. In addition, the period oftime during which chemical crosslinking of the biopolymer occurs can beshort enough to reach a target deployed viscosity within a reasonabletime (e.g., in the range of 10-60 minutes; or at most 40 minutes, 30minutes, 20 minutes, or 10 minutes) after delivery. The target deployedviscosity can be high enough to cause an agglomeration of the embolicelement 230 to remain within the internal volume of the aneurysm withoutreinforcing the neck.

In at least some cases, the biopolymer has a non-zero degree of chemicalcrosslinking within the first precursor material 203 before mixing withthe chemical crosslinking agent. This can be useful, for example, tocustomize the curing window for the embolic element 230 so that itcorresponds well with an expected amount of time needed to deliver thematerial to the aneurysm. The degree of chemical crosslinking of thebiopolymer within the first precursor material 203 before mixing withthe chemical crosslinking agent, the ratio of the biopolymer to thechemical crosslinking agent, and/or one or more other variables can beselected to cause the embolic element 230 to have a viscosity suitablefor delivery to the aneurysm via the lumen of the conduit 116 for asuitable period of time (e.g., a period within a range from 10 minutesto 40 minutes) after mixing of the first and second precursor materials203, 205. In at least some cases, the first and second precursormaterials 203, 205 are mixed in proportions that cause a weight ratio ofthe biopolymer to the chemical crosslinking agent in the resultingembolic element 230 to be within a range from 10:1 to 100:1, such asfrom 10:1 to 30:1, or from 15:1 to 50:1, or from 15:1 to 25:1. In aparticular example, the first and second precursor materials 203, 205are mixed in proportions that cause a weight ratio of the biopolymer tothe chemical crosslinking agent in the resulting embolic element 230 tobe 30:1.

Use of a biopolymer instead of an artificial polymer in the firstprecursor material 203 may be advantageous because biopolymers tend tobe more readily bioabsorbed than artificial polymers and/or for otherreasons. Furthermore, use of a chemical crosslinking agent instead of aphysical crosslinking agent (i.e., a crosslinking agent that formsnoncovalent crosslinks between chains of the biopolymer) in the secondprecursor material 205 may be advantageous because chemicallycrosslinked polymers tend to be more cohesive than physicallycrosslinked polymers and/or for other reasons. In the context of forminga tissue scaffold within an aneurysm, high cohesiveness of the embolicelement 230 may be more important than it is in other contexts to securethe cured embolic element 230 within the aneurysm 302. For example, highcohesiveness of the embolic element 230 may reduce or eliminate thepossibility of a piece of the embolic element 230 breaking free andentering a patient's intracerebral blood stream during delivery.

The first and second precursor materials 203, 205 may include othercomponents and/or the system 200 may include other precursor materialsintended for mixing with the first and second precursor materials 203,205. For example, the first, second, and/or another precursor materialmay include a physical crosslinking agent. The presence of a physicalcrosslinking agent may be useful to form physical crosslinks thatcomplement chemical crosslinks from the chemical crosslinking agent. Thecombination of chemical and physical crosslinks may enhance thecohesiveness of the embolic element 230. Suitable physical crosslinkingagents for use with chitosan-based biopolymers include βglycerophosphate, mannitol, glucose, and derivatives and analogsthereof. In these and other cases, the embolic element 230 may includemultiple chemical crosslinking agents and/or multiple physicalcrosslinking agents.

A contrast agent is another component that may be added to the precursormaterials. The presence of a contrast agent within the embolic element230 can be useful to visualize delivery of the embolic element 230 usingfluoroscopy. One problem with using conventional platinum coils inintracranial aneurysms is that the persistent radiopacity of the coilstends to interfere with visualizing other aspects of the treatment infollow-up imaging. For example, the presence of platinum coils within ananeurysm may make it difficult or impossible to detect by fluoroscopythe presence of blood-carried contrast agent that would otherwiseindicate recanalization. In at least some embodiments of the presenttechnology, a contrast agent within the embolic element 230 is selectedto provide radiopacity that diminishes over time. For example, thecontrast agent may initially be radiopaque to facilitate delivery of theembolic element 230 and then become less radiopaque to facilitatefollow-up imaging. In a particular example, the first, second, and/oranother precursor material includes iohexol or a derivative or analogthereof as a suitable contrast agent.

In animal studies, the liquid embolics of the present technology wereshown to provide (a) complete or nearly complete volumetric filling ofthe aneurysm internal volume, and (b) complete or nearly completecoverage of the aneurysm neck with new endothelial tissue. Thesefeatures, among others, are expected to result in a lower recanalizationrate than that of platinum coil treatments and faster aneurysm occlusionthan that of flow diverters. Furthermore, the injectable scaffoldmaterial is expected to be bioabsorbed and thereby reduced in volumeover time. Thus, unlike platinum coils, the injectable scaffold isexpected to have little or no long-term mass effect. Furthermore, theinjectable scaffold material can be configured to have diminishingradiopacity; therefore, when so configured it will not interfere futureCT and MRI imaging and procedures. Embodiments of the present technologycan have these and/or other features and advantages relative toconventional counterparts whether or not such features and advantagesare described herein.

In some embodiments, the embolic kit 200 and/or embolic element 230 maybe any embolic or occlusive device, such as one or more embolic coils,polymer hydrogel(s), polymer fibers, mesh devices, or combinationsthereof. The embolic kit 200 may include one or more precursors that,once mixed together, form the embolic element 230 that remains withinthe aneurysm. In some embodiments, the embolic kit 200 may include theembolic element pre-mixed.

II. Selected Methods for Treating Aneurysms

FIGS. 3A-3G depict an example method for treating an aneurysm A with thesystems 10 of the present technology. To begin, a physician mayintravascularly advance the second elongated shaft 108 towards anintracranial aneurysm (or other treatment location such as any of thosedescribed herein) with the occlusive member 102 in a low-profile state.A distal portion of the second elongated shaft 108 may be advancedthrough a neck N of the aneurysm A to locate a distal opening of thesecond elongated shaft 108 within an interior cavity of the aneurysm A.The elongated member 106 may be advanced distally relative to the secondelongated shaft 108 to push the occlusive member 102 through the openingat the distal end of the second elongated shaft 108, thereby releasingthe occlusive member 102 from the shaft 108 and allowing the occlusivemember 102 to self-expand into a first expanded state.

FIG. 3A shows the occlusive member 102 in a first expanded state,positioned in an aneurysm cavity and still coupled to the elongatedmember 106. As shown in FIG. 3A, in the first expanded state, theocclusive member 102 may assume a predetermined shape that encloses aninternal volume 130 (see FIG. 1C). In this first expanded state, theocclusive member 102 may generally conform to the shape of the aneurysmA. As illustrated in FIG. 3B with the occlusive member 102 and deliverysystem shown in cross-section, the conduit 116 may be advanced throughthe internal volume 130 of the occlusive member 102 such that a distalopening of the conduit 116 is at or distal to the aperture 126 at thedistal portion of the occlusive member 102. The embolic element 230 maybe delivered through the conduit 116 to a space between the occlusivemember 102 and an inner surface of the aneurysm wall W.

In some embodiments, the method includes mixing the first and secondprecursor materials 203, 205 (FIG. 2) to form the embolic element 230.Mixing of the first and second precursor materials 203, 205 may occurprior to introducing the embolic element 230 to the treatment system 100and/or during delivery of the embolic element through the conduit 116 tothe aneurysm. In a particular example, the first precursor material 203is loaded into one of the barrels 214, the second precursor materials205 is loaded into the other barrel 214, and the mixing syringes 208 arecoupled via the coupler 210. To mix the first and second precursormaterials 203, 205, the plungers 212 are alternately depressed, therebycausing the first and second precursor materials 203, 205 to moverepeatedly from one barrel 214 to the other barrel 214. After suitablymixing the precursor materials, the resulting embolic element 230 can beloaded into the barrel 220 of the injection syringe 216. The injectionsyringe 216 may then be coupled to a proximal end of the conduit 116 todeliver the embolic element 230 through the conduit 116 and into theaneurysm A. As the embolic element 230 passes through the lumen of theconduit 116, chemical crosslinking of the biopolymer can continue tooccur.

Still with reference to FIG. 3B, as the embolic element 230 is deliveredbetween the dome of the aneurysm A and the distal portion 132 of thewall of the occlusive member 102, pressure builds between the aneurysmwall W and the occlusive member 102. As shown in the progression ofFIGS. 3B-3D, when the forces on the occlusive member 102 reach athreshold level, the embolic element 230 pushes the distal wall 132downwardly towards the neck N of the aneurysm A. The embolic element 230exerts a substantially uniform pressure across the distal surface of theocclusive member 102 that collapses the occlusive member 102 inwardly onitself such that the rounded distal wall 132 transitions from concavetowards the neck N of the aneurysm A to convex towards the neck N. Thepressure and inversion of the distal portion of the wall 132 creates anannular fold 136 that defines the distal-most edge of the occlusivemember 102. As the occlusive member 102 continues to invert, theposition of the fold 136 moves towards the neck N, which continues untila distal-most half of the occlusive member 102 has inverted. In someembodiments, the occlusive member 102 may include one or more portionsconfigured to preferentially flex or bend such that the occlusive member102 folds at a desired longitude. Moreover, as the occlusive member 102collapses, a distance between the wall at the distal portion 132 and thewall at the proximal portion decreases, and thus the internal volume 130of the occlusive member 102 also decreases. As the occlusive member 102collapses, the conduit 116 may be held stationary, advanced distally,and/or retracted proximally.

During and after delivery of the embolic element 230, none orsubstantially none of the embolic element 230 migrates through the poresof the occlusive member 102 and into the internal volume 130. Saidanother way, all or substantially all of the embolic element 230 remainsat the exterior surface or outside of the occlusive member 102.Compression of the occlusive member with the embolic element 230provides a real-time “leveling” or “aneurysm-filling indicator” to thephysician under single plane imaging methods (such as fluoroscopy) sothat the physician can confirm at what point the volume of the aneurysmis completely filled. Additional details regarding devices, systems, andmethods for monitoring and/or confirming deployment are described belowwith reference to FIGS. 4A-5B. It is beneficial to fill as much space inthe aneurysm as possible, as leaving voids within the aneurysm sac maycause delayed healing and increased risk of aneurysm recanalizationand/or rupture. While the scaffolding provided by the occlusive member102 across the neck helps thrombosis of blood in any gaps and healing atthe neck, the substantial filling of the cavity prevents rupture acutelyand does not rely on the neck scaffold (i.e., the occlusive member 102).Confirmation of complete or substantially complete aneurysm fillingunder single plane imaging cannot be provided by conventional devices.

Once delivery of the embolic element 230 is complete, the conduit 116may be withdrawn. In some embodiments, the embolic element 230 may fillgreater than 40% of the aneurysm sac volume. In some embodiments, theembolic element 230 may fill greater than 50% of the aneurysm sacvolume. In some embodiments, the embolic element 230 may fill greaterthan 60% of the aneurysm sac volume. In some embodiments, the embolicelement may fill greater than 65%, 70%, 75%, 80%, 85%, or 90% of theaneurysm sac volume.

FIG. 3E shows a second expanded state of the occlusive member 102, shownin cross-section, with the embolic element 230 occupying the remainingvolume of the aneurysm A. FIG. 3F shows the occlusive member 102 in fullwith the embolic element 230 removed so the second shape of theocclusive member 102 is visible. As shown, the embolic element 230 maybe delivered until the occlusive member 102 is fully-collapsed such thatthe occlusive member 102 has substantially no internal volume.

In the second expanded state, the occlusive member 102 may form a bowlshape that extends across the neck of the aneurysm A. The wall of theocclusive member 102 at the distal portion may now be positioned incontact with or immediately adjacent the wall of the occlusive member102 at the proximal portion. The distal wall 132 may be in contact withthe proximal wall 134 along all or substantially all of its length. Insome embodiments, the distal wall 132 may be in contact with theproximal wall 134 along only a portion of its length, while theremainder of the length of the distal wall 132 is in close proximity—butnot in contact with—the proximal wall 134.

Collapse of the occlusive member 102 onto itself, towards the neck N ofthe aneurysm, may be especially beneficial as it doubles the number oflayers across the neck and thus increases occlusion at the neck N. Forexample, the distal wall 132 collapsing or inverting onto the proximalwall 134 may decrease the porosity of the occlusive member 102 at theneck N. In those embodiments where the occlusive member 102 is a mesh orbraided device such that the distal wall 132 has a first porosity andthe proximal wall 134 has a second porosity, deformation of the distalwall 132 onto or into close proximity within the proximal wall 134decreases the effective porosity of the occlusive member 102 over theneck N. The resulting multi-layer structure thus has a lower porositythan the individual first and second porosities. Moreover, the embolicelement 230 along the distal wall 132 provides additional occlusion. Insome embodiments, the embolic element 230 completely or substantiallycompletely occludes the pores of the adjacent layer or wall of theocclusive member 102 such that blood cannot flow past the embolicelement 230 into the aneurysm cavity. It is desirable to occlude as muchof the aneurysm as possible, as leaving voids of gaps can allow blood toflow in and/or pool, which may continue to stretch out the walls ofaneurysm A. Dilation of the aneurysm A can lead to recanalization and/orherniation of the occlusive member 102 and/or embolic element 230 intothe parent vessel and/or may cause the aneurysm A to rupture. Bothconditions can be fatal to the patient.

In those embodiments where the wall of the occlusive member 102comprises an inner and outer layer, the deformed or second shape of theocclusive member 102 forms four layers over the neck N of the aneurysm AIn those embodiments where the wall of the occlusive member 102comprises a single layer, the deformed or second shape of the occlusivemember 102 forms two layers over the neck N of the aneurysm A Aspreviously mentioned, the neck coverage provided by the doubled layersprovides additional surface area for endothelial cell growth, decreasesthe porosity of the occlusive member 102 at the neck N (as compared totwo layers or one layer), and prevents herniation of the embolic element230 into the parent vessel. During and after delivery, the embolicelement 230 exerts a substantially uniform pressure on the occlusivemember 102 towards the neck N of the aneurysm A, thereby pressing theportions of the occlusive member 102 positioned adjacent the neckagainst the inner surface of the aneurysm wall such that the occlusivemember 102 forms a complete and stable seal at the neck N.

As shown in FIG. 3G, the first coupler 112 may be detached from thesecond coupler 114 and the elongated member 106 and second elongatedshaft 108 may be withdrawn, thereby leaving the occlusive member 102 andembolic element 230 implanted within the aneurysm A.

Over time natural vascular remodeling mechanisms and/or bioabsorption ofthe embolic element 230 may lead to formation of a thrombus and/orconversion of entrapped thrombus to fibrous tissue within the internalvolume of the aneurysm A. These mechanisms also may lead to cell deathat a wall of the aneurysm and growth of new endothelial cells betweenand over the filaments or struts of the occlusive device 102.Eventually, the thrombus and the cells at the wall of the aneurysm mayfully degrade, leaving behind a successfully remodeled region of theblood vessel.

In some embodiments, contrast agent can be delivered during advancementof the occlusive member 102 and/or embolic element 230 in thevasculature, deployment of the occlusive member 102 and/or embolicelement 230 at the aneurysm A, and/or after deployment of the occlusivemember 102 and/or embolic element 230 prior to initiation of withdrawalof the delivery system. The contrast agent can be delivered through thesecond elongated shaft 108, the conduit 116, or through another catheteror device commonly used to delivery contrast agent. The aneurysm (anddevices therein) may be imaged before, during, and/or after injection ofthe contrast agent, and the images may be compared to confirm a degreeof occlusion of the aneurysm.

According to some aspects of the technology, the system 10 may compriseseparate first and second elongated shafts (e.g., microcatheters) (notshown), the first dedicated to delivery of the embolic element, and thesecond dedicated to the delivery of the occlusive member. In examplemethods of treating an aneurysm, the first elongated shaft may beintravascularly advanced to the aneurysm and through the neck such thatthat a distal tip of the first elongated shaft is positioned within theaneurysm cavity. In some embodiments, the first elongated shaft may bepositioned within the aneurysm cavity such that the distal tip of theshaft is near the dome of the aneurysm.

The second elongated shaft containing the occlusive member (such asocclusive member 102) may be intravascularly advanced to the aneurysmand positioned within the aneurysm cavity adjacent the first elongatedshaft. The occlusive member may then be deployed within the aneurysmsac. As the occlusive member is deployed, it pushes the first elongatedshaft outwardly towards the side of the aneurysm, and when fullydeployed the occlusive member holds or “jails” the first elongated shaftbetween an outer surface of the occlusive member and the inner surfaceof the aneurysm wall.

The embolic element (such as embolic element 230) may then be deliveredthrough the first elongated shaft to a position between the innersurface of the aneurysm wall and the outer surface of the occlusivemember. For this reason, it may be beneficial to initially position thedistal tip of the first elongated shaft near the dome (or more distalsurface) of the aneurysm wall. This way, the “jailed” first elongatedshaft will be secured by the occlusive member such that the embolicelement gradually fills the open space in the aneurysm sac between thedome and the occlusive member. As described elsewhere herein, thefilling of the embolic element pushes and compresses the occlusivemember against the tissue surrounding the aneurysm neck as the space inthe sac above the occlusive member is being filled from the dome to theneck. Also as described elsewhere herein, the compression of theocclusive member with the embolic element provides a “leveling oraneurysm filling indicator” which is not provided by conventional singleplane imaging methods. The filling of the embolic element may complete,for example, when it occupies about 50-80% of the volume of theaneurysm.

III. Selected Devices, Systems, and Methods for Monitoring Deployment

Proper deployment of the embolic element 230 and the occlusive member102 can be monitored and/or confirmed using one or more medical imagingtechniques, such as fluoroscopy. FIGS. 4A-5B illustrate examples ofvarious types of fluoroscopic images that may be employed by a physicianat different stages of deployment to monitor the position of theocclusive member 102 within the aneurysm A, monitor the degree offilling of the aneurysm A with the embolic element 230, and/or confirm adegree of occlusion of the aneurysm A by the deployed system. Asdescribed in greater detail below, the devices and systems of thepresent technology may be configured to provide unique visual indicatorsthat provide confirmation to the physician via one or more medicalimaging techniques regarding a degree of occlusion of the aneurysm. Asdescribed in greater detail below, the visual indicators may include aparticular change in shape of all or a portion of the occlusive member102, a particular change in relative position of one or more radiopaquemarkers on the occlusive member 102 and/or delivery system (such as theconduit 116), a particular change in shape of the embolic element 230,and others.

Although the following discussion is made with reference to thetwo-dimensional images shown in FIGS. 4A-5B, the systems and methods ofthe present technology can be employed with three-dimensional imagingtechniques. Moreover, FIGS. 4A-5B represent a two-dimensional image inwhich only a slice of the aneurysm (and devices therein) is visible.While in some cases the inner and outer layers of the occlusive member102 (when such are present) may be distinguishable from one another inthe radiographic image, in the present example the layers appear as onethick layer. As used herein, “proper deployment” or “successfuldeployment” may refer to (a) complete (e.g., greater than 80%) orsubstantially complete (e.g., greater than 50%) filling of the aneurysmA with the embolic element 230, (b) complete or substantially completeinversion or collapse of the occlusive member 102 onto itself over theneck N of the aneurysm A, (c) or both.

The occlusive member 102 may include one or more radiopaque markers,such as markers 402, 404, 406, and 114 (referred to collectively as“markers 401”) shown in FIGS. 4A-4C. The markers 401 may be disposedabout the occlusive member 102 in a specific spatial arrangement suchthat relative movement of the markers is indicative of a degree of stageof deployment of the occlusive member 102 and/or embolic element 230.The markers 401 may be positioned at any location along the occlusivemember 102. For example, the occlusive member 102 may include one ormore radiopaque markers 402 at or along its distal wall 132 (only oneshown for ease of illustration), one or more radiopaque markers 404 ator along its proximal wall 134 (only one shown for ease ofillustration), and one or more radiopaque markers 406 at or along theintermediate portion of the wall (only one shown for ease ofillustration). Moreover, the coupler 114 of the occlusive member 102 maybe radiopaque. The markers 401 may be positioned at one, some, or all ofthe layers of the occlusive member 102 (at least in those embodimentswhere the occlusive member 102 includes multiple layers). In someembodiments, the individual markers 401 may comprise a radiopaque bandor clip coupled to the one or more struts, filaments, wires, etc. of theocclusive member 102. In some embodiments, the individual markers 401may comprise a radiopaque material coated on or otherwise incorporatedinto the wall of the occlusive member 102. The individual markers 401may have the same or different shapes, lengths, and/or profiles.

In some embodiments, in addition to or instead of having one or moremarkers 401, the occlusive member 102 itself may be partially orcompletely formed of a radiopaque material, such as one or moreradiopaque wires. In the example depicted in FIGS. 4A-4C, the occlusivemember 102 is formed of a radiopaque material and also includesradiopaque markers 402, 404, 406. The occlusive member 102 is formed ofa plurality of drawn-filled tube (“DFT”) wires, which comprise a coreformed of a radiopaque material (such as platinum) surrounded by anouter non-radiopaque material (at least relative to the core material).The markers 402, 404, 406 are completely formed of a radiopaque materialand thus have a higher density of radiopaque material. As such, themarkers 402, 404, 406 appear darker than the occlusive member 102 in theimages. In some embodiments, the occlusive member 102 may have aradiopacity that is different than the radiopacity of one or more of themarkers 402, 404, 406 such that the wall of the occlusive member 102wall and the marker(s) 406 can be distinguished from one another on theradiographic image. The wall of the occlusive member 102 may be more orless radiopaque than one or more of the markers 402, 404, 406.

In some embodiments, one or more components of the delivery system mayinclude one or more radiopaque markers. For example, the conduit 116 mayinclude one or more radiopaque markers positioned along its length. Inthe embodiment depicted in FIGS. 4A-4C, the conduit 116 may include aradiopaque marker 400 positioned at or near its distal end. The conduit116 may have one or more additional markers (not shown) positioned alongits length, such as along the length of the conduit 116 that extendsthrough the interior volume 130 of the occlusive member 102.

As shown in FIG. 4A, when the occlusive member 102 is first deployed(e.g., allowed to self-expand) within the aneurysm, the radiopaquemarker(s) 402, 404, 406 of the occlusive member 102 will be in a firstposition relative to one another, and to the radiopaque marker(s) of theconduit 116. By way of example, markers 402 and 404 are separated by afirst distance di when the occlusive member 102 is first deployed. Asthe embolic element 230 is conveyed through the conduit 116 and into theaneurysm sac, the occlusive member 102 may deform as describedpreviously with respect to FIGS. 3A-3G. This deformation can cause theradiopaque marker(s) 401 carried by the occlusive member 102 to move toa second position relative to one another. For example, the physicianmay confirm progression of deployment by observing that markers 402 and404 are now separated by a distance dz. The radiopaque marker(s) 401 mayalso move relative to the radiopaque marker(s) 400 of the conduit 116,which may remain in the same or substantially the same place within theaneurysm. By comparing an image of the radiopaque markers 400 and/or 401in the first relative positions and an image of the radiopaque markers400 and/or 401 in the second relative positions, a clinician canvisually confirm that the embolic element 230 has filled a certainpercentage of the aneurysm A.

For example, according to some aspects of the technology, confirmationof sufficient filling of the aneurysm (i.e., 50% or greater) may beindicated by one or more distal wall markers 402 moving into closeproximity to one or more proximal wall markers 404 and/or touching oneor more proximal wall markers 404. Because the embolic element 230applies a generally uniform pressure across the distal wall 132 andpushes downwardly towards the neck N as it fills in the space betweenthe occlusive member 102 and the aneurysm wall, the movement of one ormore distal wall markers 402 to a position adjacent a proximal wallmarker 404 indicates to a physician that the aneurysm A is substantiallyfilled (e.g., 50% or greater) with the embolic element 230. Thisrelative positioning also indicates that the distal wall 132 is nowproviding additional occlusion at the neck N of the aneurysm and thatthe occlusive member 102 is in its second expanded shape. In someembodiments, the coupler 114 may be used as the proximal indicatorinstead of or in addition to the one or more proximal markers 404.

In some embodiments, confirmation of sufficient filling of the aneurysm(i.e., 50% or greater) may be indicated by one or more distal wallmarkers 402 moving away from the conduit marker 400 (or marker affixedto another component of the delivery system) by a predetermineddistance. For example, when the occlusive member 102 is in the firstexpanded state or shape (FIG. 4A) the distal wall marker 402 may beadjacent the conduit marker 400. In the second expanded state or shape(FIG. 4C), the distal wall marker 402 may be separated from the conduitmarker 400 by a distance that is generally equivalent to a diameter D ofthe occlusive member 102 in its expanded state while initiallypositioned in the aneurysm A. As explained above, such relativepositioning of one or more distal wall markers 402 and conduit marker400 indicates to a physician that the aneurysm A is substantially filled(e.g., 50% or greater) with the embolic element 230. This relativepositioning also indicates that the distal wall 132 is now providingadditional occlusion at the neck N of the aneurysm and that theocclusive member 102 is in its second expanded shape.

In some embodiments, one or more intermediate markers 406 may be used toconfirm and/or monitor deployment. For example, one or more intermediatemarkers 406 may be positioned at or near a desired inversion plane ofthe occlusive member 102. In the present example using a generallyspherical occlusive member 102 that deforms to assume a bowl shape, theinversion plane is at or near a midline of the occlusive member 102 inits expanded state. This is because, in a fully inverted state, thedistal half of the occlusive member 102 will lie within/conform to theproximal half of the occlusive member 102 (as shown in FIG. 4C). Assuch, the midline of the occlusive member 102 is the desired plane ofinversion. The occlusive member 102 may be radiopaque (as shown in FIGS.4A-4C), but to a lesser extent than the intermediate marker(s) 406 suchthat the occlusive member 102 wall and the marker(s) 406 can bedistinguished from one another on the radiographic image. As such, animage showing the top edge 136 (FIG. 4C) of the occlusive member 102adjacent or at the intermediate marker(s) 406 may indicate that theaneurysm A is substantially filled (e.g., 50% or greater) with theembolic element 230. This relative positioning also indicates that thedistal wall 132 is now providing additional occlusion at the neck N ofthe aneurysm and that the occlusive member 102 is in its second expandedshape.

The change in shape of the occlusive member 102 and/or change inposition of different portions of the occlusive member 102 relatively toone another may also indicate proper deployment. As previouslydiscussed, the occlusive member 102 assumes a first expanded shape wheninitially deployed and has a second expanded shape after deformation bythe embolic element 230. In several embodiments, the second expandedshape represents a partially or completely inverted from of the firstexpanded shape, which can be confirmed on the radiographic image byobserving the changing outline of the occlusive member 102. Forinstance, in the present example where the occlusive member 102 has afirst expanded shape that is generally spherical, an image showing aC-shape (as shown in FIG. 4C) may indicate that the desired fillingand/or deployment is complete. In a three-dimensional image, the secondexpanded shape may have a bowl shape. In some embodiments, confirmationof complete or substantially complete deployment may be indicated by thedistal wall 500 being within a predetermined distance of the proximalwall 502.

In some embodiments, proper deployment may be confirmed by observing adistance between the inverted wall (here, distal wall 132) and therelatively stationary wall (here, proximal wall 134). As shown in FIG.4C, when the distal wall 132 collapses down onto or near the proximalwall 134, the occlusive member 102 presents on the image as having twicethe thickness at the proximal portion. Moreover, as the occlusive member102 inverts, the density of the radiopaque material doubles, and thusthe doubled-over portions of the occlusive member 102 appear darker onthe image.

As shown in FIGS. 5A and 5B, in some embodiments, certain portions ofthe occlusive member 102 may be coated with a radiopaque material suchthat change in shape or orientation of those portions indicates adesired position of the occlusive member 102. For example, as shown inFIG. 5A, a distal-most half 500 of the occlusive member 102 may becoated with a radiopaque material while a proximal-most half 502 may notbe coated or may otherwise be less radiopaque than the distal half 500.As such, confirmation of complete or substantially complete deploymentmay be indicated by the more radiopaque distal wall 500 being adjacentthe proximal wall 502. For example, confirmation of complete orsubstantially complete deployment may be indicated by the distal wall500 being within a predetermined distance of the proximal wall 502.Confirmation may also be gleaned from the distal wall 500 changing inshape from flat or convex (towards the dome) of the aneurysm A toconcave.

A shape of the embolic element 230 may also provide an indication ofdeployment progress. For example, the shape of the lower (closer to theneck N) perimeter of the aneurysm A can be indicative of a degree offilling of the aneurysm with the embolic element 230 and/or degree ofdeformation of the occlusive member 102. As most aneurysms have agenerally spherical or globular shape, a lower boundary of the embolicelement 230 may have a decreasing radius of curvature as more isinjected and more of the occlusive member 102 inverts. For example, inFIG. 4B, when the aneurysm A is partially filled with the embolicelement 230 and the occlusive member 102 is only partially collapsed orinverted, the distal wall 132 has a first radius of curvature. In FIG.4C, when the aneurysm A is substantially completely or completelyfilled, the distal wall 132 has a radius of curvature less than theradius of curvature of the distal wall 132 in the partially deformedstate.

Additionally or alternatively, the degree of deployment of the occlusivemember 102 and/or degree of filling of the aneurysm A can be furtherdetermined by injecting contrast into the parent blood vessel andimaging the aneurysm to determine how much of the contrast enters theaneurysm cavity. The shape of the

The devices, systems, and methods of the present technology may beparticularly beneficial over conventional devices for two-dimensionalimaging. In two-dimensional imaging (such as fluoroscopy), the image mayreflect only a slice or elevational view of the aneurysm (and device orsubstance therein). As such, any voids or gaps in filling may not beapparent in the slice because the image slice does not transect the voidwithin the aneurysm A, or the cross-section or elevational view of thestagnated area may take on different shapes depending on how the imageis observed. A physician may have to take a plurality of images todetermine a general amount of filling in the aneurysm. In contrast, theocclusive members 102 of the present technology have a unique shape thatdynamically adjusts to the introduction of an embolic element 230 in apredictable, measurable way that indicates a degree of filling of theembolic element 230 in a single two-dimensional radiographic image.

The devices, systems, and methods disclosed herein include confirmingand/or observing various stages of deployment of the system in ananeurysm, including complete or substantially complete deployment, usingone, some, or all of the methods disclosed above.

IV. Examples of Occlusive Members

Intrasaccular treatment of saccular aneurysms having a certainmorphology (such as a wide-necked aneurysm) often requires the occlusivedevice to be oversized relative to the aneurysm to be treated to providethe radial force necessary for neck protection and stability. In severalof the foregoing embodiments, the occlusive member has a substantiallyspherical first expanded state (see, for example, FIG. 3A). Whenoversized and implanted, some of these occlusive members elongate andcause the occlusive member to protrude into the parent vessel. Toaddress this challenge and avoid or reduce elongation of the occlusivemember, in some embodiments of the present technology the occlusivemember is configured to assume a semi-collapsed shape (similar to thehemispherical shape shown in FIG. 3C) when initially deployed. However,occasionally these hemispherical occlusive members elongate during orafter deployment such that the distal portion 132 of the occlusivemember wall bows distally in the first expanded state (rather than beinggenerally flat or bowing proximally towards the proximal wall 134),before introduction of the embolic element. In such instances, theelongated shape makes subsequent inversion of the occlusive member bydelivery of the embolic element (as discussed herein) particularlychallenging.

Several embodiments of the occlusive members of the present technologyare configured to address the foregoing challenges. Several of suchembodiments, for example, are described below with respect to FIGS.6A-15B. The occlusive members detailed herein allow for sufficientoversizing without treatment-prohibitive elongation, obviate the needfor device inversion when the embolic element is delivered, reduce oreliminate protrusion of the occlusive member into the parent vessel, andprovide a good fit to the contour of the aneurysm neck.

FIG. 6A is a slightly-angled side view of an occlusive member 600configured in accordance with several embodiments of the presenttechnology. FIGS. 6B and 6C are isometric and cross-sectional views,respectively, of the occlusive member 600. Referring to FIGS. 6A-6Ctogether, the occlusive member 600 may comprise a mesh have a proximalportion 600 a configured to be positioned over a neck of the aneurysm, adistal portion 600 b, a proximal coupler 604, and a distal coupler 606.In some embodiments, the mesh is biased towards a predetermined shapewhen the mesh is in an expanded, unconstrained state. The mesh can beformed of a wall surrounding an interior region 618 and comprising afirst portion 614, a second portion 612, and an annular ridge 610. Thefirst portion 614 and the second portion 612 may be separated by adistance d that increases towards the central longitudinal axis of theocclusive member 600. In some embodiments, the distance d may begenerally constant or may decrease towards the central longitudinal axisof the device. The first portion 614 of the wall can extend between theproximal coupler 604 and the ridge 610, and the second portion 612 ofthe wall can extend between the ridge 610 and the distal coupler 606.

In contrast to the occlusive members disclosed herein having a distalwall that bows outwardly away from the interior region in the firstexpanded state (see, for example, distal wall 132 in FIG. 1C), or issubstantially flat in the first expanded state, the second portion 612of the occlusive member 600 bows inwardly towards the interior portion618 in the first expanded state, thereby forming a cavity 608 at thedistal portion 600 b of the occlusive member 600. The cavity 608, forexample, can be bound by the second portion 612 of the wall and a planelying on ridge 610. As shown in FIGS. 6A-6C, all or a portion of thedistal coupler 606 may thus be positioned within the cavity 608, belowthe plane defined by the ridge 610. In some embodiments, the occlusivemember 600 and/or mesh includes a recessed portion 616 at the proximalportion 600 a that surround all or a portion of the proximal coupler604. In some embodiments, the occlusive member 600 and/or mesh does notinclude a recessed portion 616 at the proximal portion 600 a.

Because the second portion 612 bows proximally, the occlusive member 600is less likely to elongate when deployed in the aneurysm and/orelongates less (as compared to the occlusive members with an outward bowor substantially flat distal wall). In addition, because the bowedsecond portion 612 mimics the semi-collapsed states discussed herein(for example with reference to FIGS. 1A-5B), the occlusive member 600does not have to rely on the proximally-directed forces applied by theembolic element to cause inversion of the occlusive member 600. Instead,the embolic element can fill the space between the second portion 612and the aneurysm wall with or without causing the second portion 612 tomove towards the first portion 614.

In some embodiments, for example as shown in FIGS. 6A-6C, the occlusivemember 600 and/or mesh is formed of a plurality of braided filaments602, each having first and second ends and a length measuredtherebetween. In contrast to the occlusive members disclosed herein inwhich the first and second ends of the filaments are secured relative toone another at the same location (such as the proximal coupler), thefirst and second ends of the filaments 602 forming occlusive member 600are secured relative to one another at separate couplers. For example,the first ends of the filaments 602 can be secured relative to oneanother at the proximal coupler 604, and the second ends of thefilaments 602 can be secured relative to one another at the distalcoupler 606. As such, the second ends of the filaments 602 terminatewithin the cavity 608, below the plane defined by the ridge 610. Theresulting mesh structure thus has a “single layer” deliveryconfiguration in which the distal coupler 606 is longitudinally spacedapart from the proximal coupler 604 by a distance greater than thelongitudinal distance between the distal and proximal couplers 606, 604when the occlusive member 600 is in an expanded state. As such, when theocclusive member 600 is in a delivery configuration, the occlusivemember 600 is elongated such that no portion or substantially no portionof any filament 602 radially overlaps another portion of the samefilament 602. When the occlusive member 602 is released from thedelivery sheath, the proximal and distal couplers 604, 606 movelongitudinally closer together, thus creating the bowed second portion612 and cavity 608.

The single layer delivery configuration of occlusive member 600 (as wellas occlusive member 700, occlusive member 800, occlusive member 900,etc.) advantageously allows for a mesh having a lower delivery profile,and thus enables delivery of the occlusive member through smallerdiameter delivery catheters as compared to occlusive members havingdouble layer delivery configurations (for example, occlusive member 102,occlusive member 1000, occlusive member 1100, occlusive member 1300,etc.) or quadruple layer delivery configurations (for example, occlusivemember 1400, occlusive member 1500, etc.).

In some embodiments, the second portion 612 of the wall may have acontour and/or shape that substantially follows the contour and/or shapeof the first portion 614 of the wall, or the first and second portions612, 614 may have different contours and/or shapes. In these and otherembodiments, a radius of curvature of all or a portion of the secondportion 612 of the wall may be different than the radius of curvature ofall or a portion of the first portion 614 of the wall. In these andother embodiments, the second portion 612 of the wall may have a radiusof curvature that is greater than, less than, or substantially equal tothe radius of curvature of the first portion 614 of the wall. The secondportion 612 of occlusive member 600 can have a substantially constantslope along its length (i.e., between the ridge 610 and the distalcoupler 606), or all or a portion of the length may be convex towardsthe aneurysm wall (while still maintaining cavity 608), and/or all or aportion of the length may be concave towards the aneurysm wall.

The mesh of occlusive member 600 may be formed of metal wires, polymerwires, or both, and the wires may comprise a resilient material and/or amaterial having shape memory and/or superelastic properties. The meshmay be formed of 24, 32, 36, 48, 64, 72, 96, 128, or 144 filaments. Themesh may be formed of a range of filament or wire sizes, such as wireshaving a diameter of from about 0.0004 inches to about 0.0020 inches, orof from about 0.0009 inches to about 0.0012 inches. In some embodiments,each of the wires or filaments have a diameter of about 0.0004 inches,about 0.0005 inches, about 0.0006 inches, about 0.0007 inches, about0.0008 inches, about 0.0009 inches, about 0.001 inches, about 0.0011inches, about 0.0012 inches, about 0.0013 inches, about 0.0014 inches,about 0.0015 inches, about 0.0016 inches, about 0.0017 inches, about0.0018 inches, about 0.0019 inches, or about 0.0020 inches. In someembodiments, all of the filaments of the braided mesh may have the samediameter. For example, in some embodiments, all of the filaments have adiameter of about 0.001 inches. In some embodiments, some of thefilaments may have different cross-sectional diameters. For example,some of the filaments may have a slightly thicker diameter to impartadditional strength to the braided layers. In some embodiments, some ofthe filaments can have a diameter of about 0.001 inches, and some of thefilaments can have a diameter of greater than 0.001 inches. The thickerfilaments may impart greater strength to the braid without significantlyincreasing the device delivery profile, with the thinner wires offeringsome strength while filling-out the braid matrix density.

FIGS. 7 and 8 are cross-sectional views of different occlusive members700, 800 configured in accordance with several embodiments of thepresent technology. Several features of the occlusive member 700 shownin FIG. 7 can be generally similar to the features of occlusive member600. The occlusive member 700 shown in FIG. 7, however, has a secondportion 712 that includes a region that is concave towards the interiorregion 718 along most of its length, and has a wider ridge 710 thanridge 610. Several features of the occlusive member 800 shown in FIG. 8can be generally similar to the features of occlusive member 600. Theocclusive member 800 of FIG. 8, however, has less separation between thefirst and second portions 812, 814, and a generally constant distance dbetween the first and second portions 812, 814. As a result, theocclusive member 800 has a bowl-shaped configuration in the firstexpanded state.

FIG. 9A is a side view of an occlusive member 900 configured inaccordance with several embodiments of the present technology. Severalfeatures of the occlusive member 900 shown in FIG. 9A can be generallysimilar to the features of occlusive member 600. In FIG. 9A, theocclusive member 900 has a cavity 908 that is fairly shallow. FIG. 9B isa side view of the occlusive member of FIG. 9A shown in an elongated,expanded state in a transparent tube. As shown in FIG. 9B, the secondportion 912 extends distally such that the distal portion 900 b isfarther from the proximal portion 900 a than when the occlusive member900 is in the first expanded state (FIG. 9A).

It will be appreciated that occlusive members of the present technologyhaving a single layer delivery configuration can have different shapes,sizes, and configurations and are not limited to those embodimentsdepicted in the drawings. Moreover, an elongate shaft for delivery ofthe embolic element may be positioned through one or both of theproximal and distal couplers.

FIGS. 10A, 10B and 10C are isometric, cross-sectional, and side views,respectively, of an occlusive member 1000 configured in accordance withseveral embodiments of the present technology. Referring to FIGS.10A-10C together, the occlusive member 1000 may comprise a mesh have aproximal portion 1000 a configured to be positioned over a neck of theaneurysm, a distal portion 1000 b, and a proximal coupler (not depictedin FIGS. 10A-10C). In some embodiments, the mesh is biased towards apredetermined shape when the mesh is in an expanded, unconstrainedstate. The mesh can be formed of a wall surrounding an interior regionand comprising a first portion 1014, a second portion 1012, and anannular ridge 1010. The first portion 1014 and the second portion 1012may be separated by a distance d. In some embodiments, the distance dmay be generally constant or slightly increase towards the centrallongitudinal axis of the device. The first portion 1014 of the wall canextend between the proximal coupler and the ridge 1010, and the secondportion 1012 of the wall can extend between the ridge 1010 and theproximal coupler.

In contrast to the occlusive members disclosed herein having a distalwall that bows outwardly away from the interior region in the firstexpanded state (see, for example, distal wall 132 in FIG. 1C), or issubstantially flat in the first expanded state, the second portion 1012of the occlusive member 1000 bows inwardly towards the interior portionin the first expanded state, thereby forming a cavity 1008 at the distalportion 1000 b of the occlusive member 1000, thereby forming a bowl orchalice shape. The cavity 1008, for example, can be bound by the secondportion 1012 of the wall and a plane lying on ridge 1010.

Because the second portion 1012 is biased proximally, the occlusivemember 1000 is less likely to elongate when deployed in the aneurysmand/or elongates less (as compared to the occlusive members with anoutward bow or substantially flat distal wall). In addition, because thebowed second portion 1012 mimics the semi-collapsed states discussedherein (for example with reference to FIGS. 1A-5B), the occlusive member600 does not have to rely on the proximally-directed forces applied bythe embolic element to cause inversion of the occlusive member 1000.Instead, the embolic element can fill the space between the secondportion 1012 and the aneurysm wall with or without causing the secondportion 1012 to move towards the first portion 1014.

In some embodiments, for example as shown in FIGS. 10A-10C, theocclusive member 1000 and/or mesh is formed of a plurality of braidedfilaments 1002, each having first and second ends and a length measuredtherebetween. In contrast to occlusive member 600, the first and secondends of the filaments of occlusive member 1000 are secured relative toone another at the same location (the proximal coupler, not shown). Theproximal coupler is configured to be attached to the first and secondends at the distal-most region where the first and second ends cometogether. As shown in FIGS. 10A-10C, the second ends come together atthe bottom of the cavity 1008 and form a proximally-extending columnthat extends into the collected first ends. The resulting mesh structurethus has a “double layer” delivery configuration in which the first andsecond portions 1014, 1012 of the wall radially overlap one another whenthe occlusive member 1000 is in a low-profile state and contained withina delivery catheter.

FIGS. 11A and 11B are side and cross-sectional views, respectively, ofan occlusive member 1100 configured in accordance with severalembodiments of the present technology. As shown in FIGS. 11A and 11B,the occlusive member 1100 can have a double-layer deliveryconfiguration. In some embodiments, the occlusive member 1100 has afirst portion 1114 that extends proximally from the ridge 1110 thenturns and extends distally towards the proximal coupler 1104. As such,the first and second portions extend longitudinally towards one anotherto meet at the proximal coupler 1104. FIG. 12 is a side view of theocclusive member of FIGS. 11A and 11B shown in an expanded, elongatedconfiguration in a transparent tube.

FIGS. 13A and 13B are side and cross-sectional views, respectively, ofan occlusive member 1300 configured in accordance with severalembodiments of the present technology. As shown in FIGS. 13A and 13B,the occlusive member 1300 can have a double-layer deliveryconfiguration. In contrast to occlusive member 1100, occlusive member1300 has a generally constant distance d between the first and secondportions 1314, 1312 such that the occlusive member 1300 has a disc-shapein the first expanded state.

FIGS. 14A and 14B are side and cross-sectional views, respectively, ofan occlusive member 1400 configured in accordance with severalembodiments of the present technology. As shown in FIGS. 14A and 14B,the occlusive member 1400 has a “quadruple layer” delivery configurationin which portions 1414 a, 1414 b, 1412 a, and 1412 b radially overlapone another when the occlusive member 1400 is in a low profile state ina delivery catheter. In contrast to several of the previous embodiments,the ridge 1410 is formed by a bend in the first portion 1414 a, and doesnot correspond to where the first and second portions 1414, 1412 meet.Instead, the first and second portions 1414, 1412 meet at fold 1413,which lies within the cavity 1408.

FIGS. 15A and 15B are side and cross-sectional views, respectively, ofan occlusive member 1500 configured in accordance with severalembodiments of the present technology. As shown in FIGS. 15A and 15B,the occlusive member 1500 has a “quadruple” layer deliveryconfiguration. The occlusive member 1500 has a second portion 1512 witha substantially constant slope.

V. Selected Methods of Manufacturing

The present technology relates to occlusive devices and associatedmethods of manufacturing. Specific details of these and other methods ofmanufacturing the mesh structures of the present technology aredescribed below with reference to FIGS. 16-21D.

In some embodiments, a forming assembly of the present technologycomprises multiple forming members. For example, FIG. 16 depicts aforming assembly 1600 (or “assembly 1600”) in accordance with severalembodiments of the present technology, shown in an unassembled state. Asshown in FIG. 16, the assembly 1600 can comprise a first member 1602 anda second member 1604 (collectively “members 1602, 1604”). The members1602, 1604 may be configured to be positioned adjacent one another sothat when a mesh is positioned between the members 1602, 1604, the meshsubstantially conforms to a surface of each of the members 1602, 1604. Ashape of each of the members 1602, 1604 may be based on a desiredpredetermined shape of the occlusive device and/or the geometry of theaneurysm to be treated. Suitable shapes of the members 1602, 1604include, but are not limited to, spherical and non-spherical shapes,cylinders, hemispheres, polyhedrons (e.g., cuboids, tetrahedrons (e.g.pyramids), octahedrons, prisms, etc.), oblate spheroids, plates (e.g.,discs, polygonal plates), bowls, non-spherical surfaces of revolution(e.g., toruses, cones, cylinders, or other shapes rotated about a centerpoint or a coplanar axis), and combinations thereof.

According to some embodiments, for example as shown in FIG. 16, thefirst member 1602 has a generally globular shape. The first member 1602may have a lumen 1606 extending through at least a portion of the firstmember 1602. For example, as shown in FIG. 16, the lumen 1606 may extendthrough a thickness of the first member 1602. Further, the lumen 1606may extend along a longitudinal axis of the first member 1602. In someembodiments, a diameter of the lumen 1606 is based, at least in part, ona diameter of the tubular mesh. Additionally or alternatively, thediameter of the lumen 1606 may be selected to enable the first member1602 to receive at least a portion of an elongate member, such as amandrel, within the lumen 1606. The first member 1602 can have a firstmating surface 1608 comprising at least a portion of an outer surface ofthe first member 1602. According to several embodiments, the firstmating surface 1608 is configured to influence a shape of the contouredmesh produced as described herein, as at least a portion of the mesh mayconform to the first mating surface 1608 during the shape-settingprocess.

As shown in FIG. 16, the second member 1604 can have a generallyhemispherical shape defining a cavity 1610 with a second mating surface1612 (e.g., a hollow hemispherical shape). The second mating surface1612 may be arcuate (see FIG. 16). The second member 1604 may beconfigured to receive at least a portion of the first member 1602 withinthe cavity 1610 of the second member 1604. Accordingly, in someembodiments, the second mating surface 1612 has a shape based on a shapeof the first mating surface 1608 of the first member 1602. The secondmember 1604 depicted in FIG. 16 comprises a thickness 1614 between anouter surface 1616 of the second member 1604 and the second matingsurface 1612. The thickness 1614 can be uniform or nonuniform across thesecond member 1604. The second member 1604 can comprise a lumen 1618extending through the second member 1604 and/or along a longitudinalaxis of the second member 1604. The lumen 1618 can comprise a constantdiameter or the diameter of the lumen 1618 may vary across a length ofthe lumen 1618. In some embodiments, a first portion of the lumen 1618may have a first diameter sufficient to receive at least a portion of amandrel and/or the mesh within the first portion of the lumen 1618. Asecond portion of the lumen 1618 may have a second diameter that issubstantially equivalent to a diameter of the lumen 1606 of the firstmember 1602. Although not depicted in FIG. 16, the second member 1604may comprise a protrusion extending from the outer surface 1616 and/orthe second mating surface 1612. The protrusion may be configured toinfluence the shape of the mesh, facilitate coupling of the mesh to thesecond member 1604, align the mesh with the second member 1604, etc.

FIGS. 17A-17D depict various stages of an example method for forming acontoured mesh of an occlusive device using the assembly 1600 and a mesh1720 comprising a first end portion 1720 a, a second end portion 1720 b,and intermediate portion 1720 c therebetween. The mesh 1720 can have atubular configuration with a lumen 1722 extending along a length of themesh 1720. Although the mesh 1720 shown in FIG. 17A comprises a singlelayer, the mesh 1720 may comprise any suitable number of layers, aspreviously described. A mesh used to form an occlusive device of thepresent technology may initially comprise a tubular configuration, suchas a braided mesh tube. The mesh tube may comprise one layer, twolayers, three layers, or more. The number of layers may be selectedbased on a desired property of the occlusive device. For example, a meshcomprising two layers may have a lower porosity and may be able to applygreater radial force than a single-layered mesh. In some embodiments,the mesh is everted or inverted such that the tubular mesh comprisesinner and outer layers meeting at a fold.

As shown in FIG. 17A, the method can include positioning at least afirst portion 1720 c 1 of the intermediate portion 1720 c of the mesh1720 over the second member 1604 so that the first portion 1720 c 1substantially conforms to the outer surface 1616 of the second member1604 and the first and second end portions 1720 a, 1720 b extend awayfrom the second member 1604 in opposing directions. Positioning thefirst portion 1720 c 1 of the intermediate portion 1720 c of the mesh1720 over the second member 1604 may comprise stretching the mesh 1720.

According to some embodiments, for example as shown in FIG. 17A, atleast a portion of a mandrel 1724 is positioned within the lumen 1722 ofthe mesh 1720 and/or the lumen 1618 of the second member 1604. Themandrel 1724 can have a generally tubular shape with a circularcross-sectional shape. Additionally or alternatively, the mandrel 1724may have another suitable cross-sectional shape including, but notlimited to, rectangular, ovoidal, etc. The cross-sectional shape of themandrel 1724 may be constant along a length of the mandrel 1724 or mayvary along the length of the mandrel 1724. The mandrel 1724 can have asubstantially constant thickness along the length of the mandrel 1724 orthe thickness of the mandrel 1724 may vary along its length. In someembodiments, a first coupling element 1726 is employed to couple atleast a portion of the mesh 1720 to the mandrel 1724 so that the mesh1720 substantially conforms to the shape of the mandrel 1724. The firstcoupling element 1726 may removably or permanently couple to the mesh1720 and/or mandrel. As shown in FIG. 17A, the first coupling element1726 may circumferentially surround the mesh 1720. The first couplingelement 1726 may be, for example, a wire tie, a coil, adhesive, a weld,a marker band, and/or other suitable coupling elements. The firstcoupling element 1726 may be radiopaque to facilitate visualization ofthe occlusive device. In some embodiments, multiple coupling elements1726 are coupled to multiple portions of the mesh.

Moreover, one or more coupling elements may be employed to facilitateconforming the mesh 1720 to the first member 1602 and/or the secondmember 1604. For example, as shown in FIG. 17B, a second couplingelement 1728 can be coupled to the mesh 1720 at a position adjacent tothe second mating surface 1612 of the second member 1604 such that asecond portion 1720 c 2 of the intermediate portion 1720 c of the mesh1720 is positioned within the cavity 1610 of the second member 1604. Asdescribed herein with reference to the first coupling element 1726, thesecond coupling element 1728 may be, for example, a wire tie, a coil,adhesive, a weld, a marker band, and/or other suitable couplingelements. The second coupling element 1728 may be removably orpermanently coupled to the mesh 1720, the mandrel 1724, and/or thesecond member 1604. As shown in FIG. 17B, the second portion 1720 c 2 ofthe intermediate portion 1720 c of the mesh 1720 may not exactly conformto the second mating surface 1612 of the second member 1604. In someembodiments, additional coupling elements may be employed to cause thesecond portion 1720 c 2 to substantially conform to the second matingsurface 1612 of the second member 1604. Alternatively or additionally,as described herein the first member 1602 may be at least partiallyreceived within the cavity 1610 of the second member 1604 to cause thesecond portion 1720 c 2 of the intermediate portion 1720 c of the mesh1720 to conform to the second mating surface 1612 of the second member1604.

In some embodiments, for example as shown in FIG. 17B, at least aportion of the first end portion 1720 a of the mesh 1720 is positionedwithin the lumen 1606 of the first member 1602. Additionally oralternatively, at least a portion of the mandrel 1724 may be positionedwithin the lumen 1606 of the first member 1602 to facilitate aligningthe first and second members 1602, 1604 and/or to facilitate positioningthe first end portion 1720 a of the mesh 1720 within the lumen 1606 ofthe first member 1602. In some embodiments, the lumen 1606 of the firstmember 1602 is configured to radially constrain the tubular first endportion 1720 a of the mesh 1720 during the shape-setting process.

As shown in FIG. 17C, the method may include positioning the firstmember 1602 at least partially within the cavity 1610 of the secondmember 1604 so that the second portion 1720 c 2 of the intermediateportion 1720 c of the mesh 1720 substantially conforms to the secondmating surface 1612 of the second member 1604 and/or the first matingsurface 1608 of the first member 1602. In some embodiments, the secondportion 1720 c 2 is compressed between the first and second members1602, 1604. The first and second members 1602, 1604 may be fixed inplace prior to setting a shape of the mesh 1720.

According to some embodiments, setting a shape of the mesh 1720comprises subjecting the assembly 1600 and the mesh 1720 to a heattreatment procedure. One example of a heat treatment procedure caninclude heating the assembly 1600 and the mesh 1720 to a selectedtemperature (such as, but not limited to, between 540 and 660 degreescentigrade) for a selected period of time (such as, but not limited to,between 5 and 15 minutes), followed by rapid cooling. The rapid coolingcan be achieved by any suitable cooling procedure such as, but notlimited to water quench or air-cooling. In other examples, the time andtemperature for heat treatment can be different than those discussedabove, for example, based upon the desired material properties of theocclusive device. In particular examples, the heat treatment proceduremay be carried out in an air or vacuum furnace, salt bath, fluidizedsand bed or other suitable system. The heat treatment procedure maycomprise a single procedure or multiple procedures. After completing theheat treatment, the mesh 1720 has a desired contoured shape andconfiguration (e.g., corresponding substantially to the assembly 1600).In other examples, other suitable heat-treating procedures may beemployed including, but not limited to resistive heating or heating byrunning a current though the mesh 1720. In some embodiments, setting ashape of the mesh 1720 comprises a heat-free procedure such asmechanical deformation.

The contoured mesh 1720 may be separated and removed from the assembly1600. In some embodiments, the first coupling element 1726 and/or thesecond coupling element 1728 may be removed from the mesh 1720.Alternatively, one or both of the first and second coupling elements1726, 1728 may remain attached to the mesh 1720. One or more additionalpost processing operations may be provided on the contoured mesh 1720,including, but not limited to abrasive grit blasting, shot peening,polishing, chemical etching, electropolishing, electroplating, coating,ultrasonic cleansing, sterilizing or other cleaning or decontaminationprocedures.

FIG. 17D depicts a cross-sectional view of the contoured mesh 1720separated from the assembly 1600 and having a predetermined shape in anexpanded, unconstrained state. The first end portion 1720 a and thesecond end portion 1720 b of the contoured mesh 1720 may each comprise agenerally tubular configuration. As shown in FIG. 17D, the first portion1720 c 1 of the intermediate portion 1720 c of the mesh 1720 may have ashape based on the outer surface 1616 of the second member 1604 and thesecond portion 1720 c 2 of the intermediate portion 1720 c of the mesh1720 may have a shape based on the first and second mating surfaces1608, 1612. Accordingly, the intermediate portion 1720 c of the mesh1720 may form a dual-layered sidewall that encloses an open volume. Thedual-layered sidewall may have a generally hollow, hemispherical shape,as shown in FIG. 17D. Moreover, the dual-layered sidewall may enclose anopen volume having a substantially hemispherical shape. As such, thethickness 1614 of the second member 1604 influences the size of the openvolume enclosed by the contoured mesh 1720. As shown in FIG. 17D and aspreviously described, the first coupling element 1726 and/or the secondcoupling element 1728 may remain coupled to the contoured mesh 1720.Prior to deployment of the occlusive device, the contoured mesh 1720 maybe coupled to additional components (e.g., embolic materials, couplingelements, etc.) and/or assembled within a delivery system.

Although FIGS. 16-17D depict first and second members 1602, 1604 withgenerally globular and hemispherical shapes, respectively, members of aforming assembly of the present technology may each comprise anysuitable shape, as previously described. For example, FIGS. 18A and 18Bdepict isometric and cross-sectional views, respectively, of a formingmember 1800 configured in accordance with several aspects of the presenttechnology. The forming member 1800 shown in FIGS. 18A and 18B may beused to form a dual-layered, contoured mesh having an open first endportion and a closed second end portion that is positioned at an anglewith respect to the first end portion. The forming member 1800 maycomprise a first surface 1802, a second surface 1804 opposite the firstsurface 1802 along a thickness 1806 of the forming member 1800, and asidewall 1808 therebetween. In some embodiments, the first and secondsurfaces 1802, 1804 are generally circular and/or the sidewall 1808 isgenerally annular such that the forming member 1800 has a generallycylindrical shape. However, the forming member 1800 may comprise anysuitable shape including, but not limited to, spherical, non-spherical,cylindrical, hemispherical, polyhedron (e.g., cuboid, tetrahedron (e.g.pyramids), octahedron, prism, etc.), oblate spheroid, plate (e.g., disc,polygonal plate), bowl, non-spherical surface of revolution (e.g.,torus, cone, or another shape rotated about a center point or a coplanaraxis), and combinations thereof. The thickness 1806 of the formingmember 1800 may be constant along a length of the forming member 1800 ormay vary along the length of the forming member 1800. As previouslydescribed, the thickness 1806 of the forming member 1800 can influence asize of an open volume of a contoured mesh formed with the formingmember 1800. The forming member 1800 can comprise a lumen 1810 extendingat least partially through the forming member 1800 between the first andsecond surfaces 1802, 1804 and/or along a longitudinal axis of theforming member 1800. As described herein, the lumen 1810 may compriseany suitable length and diameter.

FIGS. 19A-19C depict various stages of an example method for forming acontoured mesh of an occlusive device using the forming member 1800 anda single-layer, tubular mesh 1920 having a first end portion 1920 a, asecond end portion 1920 b, an intermediate portion 402 c therebetween,and a lumen 1922 extending along a length of the mesh 1920. As shown inFIG. 19A, the method may include positioning the intermediate portion1920 c of the mesh 1920 within the lumen 1810 of the forming member 1800so that the first end portion 1920 a of the mesh 1920 extends away fromthe first surface 1802 of the forming member 1800 in a first directionand the second end portion 1920 b of the mesh 1920 extends away from thesecond surface 1804 of the forming member 1800 in a second directionthat is opposite the first direction. In some embodiments (see FIG.19A), a mandrel 1924 is positioned within the lumen 1922 of the mesh1920 and/or the lumen 1810 of the forming member 1800.

As shown in FIG. 19B, the method may comprise everting the mesh 1920 toposition a first portion 1920 a 1 of the first end portion 1920 a of themesh 1920 over the first surface 1802 of the forming member 1800 and asecond portion 1920 a 2 of the first end portion 1920 a of the mesh 1920over the sidewall 1808 of the forming member 1800. In some embodiments,for example as shown in FIG. 19B, a coupling element 1926 is coupled tothe mesh 1920 and/or the mandrel 1924 to cause a third portion 1920 a 3of the first end portion 1920 a of the mesh 1920 to substantiallyconform to the second surface 1804 of the forming member 1800. Asdescribed herein, the coupling element 1926 may be, for example, a wiretie, adhesive, a weld, a marker band, and/or other suitable couplingelements. As shown in FIG. 19B, the coupling element 1926 maycircumferentially surround the mesh 1920 and/or the mandrel 1924.Although FIG. 19B shows the coupling element 1926 coupled to only aportion of the mesh 1920, the coupling element 1926 may be coupled toany length of the mesh 1920 and/or mandrel 1924. The coupling element1926 can be positioned adjacent the second surface 1804 of the formingmember 1800, as shown in FIG. 19B, so that the third portion 1920 a 3 ofthe first end portion 1920 a of the mesh 1920 extends along asubstantially straight path between the sidewall 1808 of the formingmember 1800 and the coupling element 1926, so that the third portion1920 a 3 substantially conforms to the second surface 1804 of theforming member 1800. However, in some embodiments, the coupling element1926 may be positioned further from the second surface 1804 of theforming member 1800 so that the third portion 1920 a 3 of the first endportion 1920 a of the mesh 1920 extends along a substantially curvedpath between the sidewall 1808 of the forming member 1800 and thecoupling element 1926. In several embodiments, no coupling elements arecoupled to the mesh 1920. Additionally or alternatively, another formingmember can be used to cause the mesh 1920 to conform to the formingmember 1800 and/or to a desired shape. In any case, a fourth portion1920 a 4 of the first end portion 1920 a of the mesh 1920 extends awayfrom the second surface 1804 of the forming member 1800 in the seconddirection. As previously described, setting a shape of the mesh 1920 maycomprise subjecting the forming member 1800 and the mesh 1920 to a heattreatment procedure.

FIG. 19C depicts the dual-layered, contoured mesh 1920 resulting fromthe method depicted in FIGS. 19A and 19B and separated from the formingmember 1800. The contoured mesh 1920 comprises a closed end portion 1920d formed by the intermediate portion 1920 c and the first, second, andthird portions 1920 a 1, 1920 a 2, 1920 a 3 of the first end portion1920 a of the mesh 1920. The contoured mesh 1920 also comprises an openend portion 1920 e formed by the fourth end portion 1920 a 4 of thefirst end portion 1920 a of the mesh 1920 and the second end portion1920 b of the mesh 1920. As shown in FIG. 19C, the open end portion 1920e of the mesh 1920 may have a substantially tubular configuration andthe closed end portion 1920 d of the mesh 1920 may be disposed at anangle to the open end portion 1920 e. The closed end portion 1920 d ofthe mesh 1920 encloses an open volume. In some embodiments, the openvolume is substantially disc shaped. As previously described, the sizeof the open volume may be based, at least in part, on the thickness 1806of the forming member 1800. The coupling element 1926 may remainpositioned around the mesh 1920 (see FIG. 19C) or may be removed.

According to some embodiments, setting a shape of a mesh to produce acontoured mesh may comprise a single shape-setting procedure. However,in certain embodiments setting a shape of the mesh may comprise two ormore shape-setting procedures (e.g., two or more heat treatmentprocesses). For example, a first contoured mesh (e.g., mesh 1920 shownin FIG. 19C) produced from a first shape-setting procedure using a firstforming assembly or member (e.g., forming member 1800) may be coupled toa second forming assembly or member, such as forming assembly 2000 (or“assembly 2000”) depicted in FIGS. 20A and 20B, and subjected to asecond shape-setting procedure to produce a second contoured mesh. Theassembly 2000 shown in FIGS. 20A and 20B comprises a first member 2002and a second member 2003. The first member 2002 has a first surface2004, a second surface 2006 opposite the first surface 2004 along athickness 2008 of the first member 2002, and a sidewall 2010therebetween. As shown in FIG. 20A, the first and second surfaces 2004,2006 may be generally rectangular such that the first member 2002 has ashape generally corresponding to a rectangular prism. The first member2002 can comprise a lumen 2012 extending at least partially through thethickness 2008 of the first member 2002. As shown in FIGS. 20A and 20B,in some embodiments, a diameter of the lumen 2012 may vary across thethickness 2008 of the first member 2002. For example, the lumen 2012 maycomprise a first portion 2012 a having a first diameter and a secondportion 2012 b having a second diameter different than the firstdiameter. The first portion 2012 a of the lumen 2012 can be configuredto receive at least a portion of the second member 2003 and/or the mesh.The second portion 2012 b of the lumen 2012 can be configured to receiveat least a portion of a mandrel and/or the mesh.

Similarly, the second member 2003 has a first surface 2014, a secondsurface 2016 opposite the first surface 2014 along a thickness 2018 ofthe second member 2003, and a sidewall 2020 therebetween. The secondmember 2003 may also have shape generally corresponding to a rectangularprism or another suitable shape. The thickness 2018 of the second member2003 can be the same as the thickness 2008 of the first member 2002 ormay differ from the thickness 2008 of the first member 2002. As shown inFIGS. 20A and 20B, in some embodiments the second member 2003 comprisesa protrusion 2022 extending away from the first surface 2014 of thesecond member 2003 in a first direction. Although the protrusion 2022 isdepicted as substantially cylindrical in FIG. 20A, the protrusion 2022can have any suitable shape, based on a desired shape of the resultingcontoured mesh. The second member 2003 can further comprise a lumen 2024extending along the thickness 2018 of the second member 2003 between thefirst and second surfaces 2014, 2016. The lumen 2024 may have a constantdiameter (see FIGS. 20A and 20B) or may vary in diameter along thethickness 2018 of the second member 2003. The lumen 2024 can beconfigured to receive at least a portion of the mesh and/or a mandrel.

FIGS. 21A-21C depict various stages of an example method for contouringa mesh 2120 using the assembly 2000. The mesh 2120 may be a contouredmesh that was previously shape-set. For example, the dual-layered mesh2120 shown in FIGS. 21A-21C has a shape similar to the shape of the mesh1920 shown in FIG. 19C. The mesh 2120 comprises a closed end portion2120 d and an open end portion 2120 e disposed at an angle to the closedend portion 2120 d. In other examples, the assembly 2000 may be used tocreate a contoured mesh from a mesh with a shape (e.g., a tubular shape)different from the shape of mesh 2120 shown in FIGS. 21A-21C. Asdepicted in FIG. 21A, at least a portion of the open end portion 2120 eof the mesh 2120 can be positioned within the lumen 2024 of the secondmember 2003 so that at least a portion of the closed end portion 2120 dof the mesh 2120 is positioned over the protrusion 2022 of the secondmember 2003. As described herein, in some embodiments a mandrel 624 ispositioned within a lumen of the mesh 2120 and/or the lumen 2024 of thesecond member 2003. Additionally or alternatively, one or more couplingelements may be coupled to the mesh 2120, as described herein. The oneor more coupling elements may be coupled to the mesh 2120 before settinga shape of the mesh 2120, while setting a shape of the mesh 2120, orafter setting a shape of the mesh 2120. The one or more couplingelements may be coupled to the mesh 2120 while the mesh 2120 conforms tothe assembly 2000 and/or after the mesh 2120 has been removed from theassembly 2000.

As shown in FIG. 21B, the method may include causing the closed endportion 2120 d of the mesh 2120 to substantially conform to theprotrusion 2022 and/or the first surface 2014 of the second member 2003.For example, as shown in FIG. 21B, the method may include positioningthe first member 2002 adjacent to the second member 2003 so that a firstportion 2120 d 1 of the closed end portion 2120 d of the mesh 2120 andat least a portion of the protrusion 2022 are received within the firstportion 2012 a of the lumen 2012 of the first member 2002. A secondportion 2120 d 2 of the closed end portion 2120 d of the mesh 2120 maysubstantially conform to a sidewall of the protrusion and a thirdportion 2120 d 3 of the closed end portion 2120 d of the mesh 2120 maysubstantially conform to the first surface 2014 of the second member2003 and the second surface 2006 of the first member 2002. As previouslydescribed, in some embodiments at least a portion of the mandrel 624 maybe positioned within the lumen 2012. In some embodiments, the mesh 2120is compressed between the first and second members 2002, 2003. The firstand second members 2002, 2003 may be fixed in place prior to setting ashape of the mesh 2120. As described herein, setting a shape of the mesh2120 may comprise subjecting the assembly 2000 and mesh 2120 to a heattreatment procedure.

FIG. 21C depicts the dual-layered, contoured mesh 2120 resulting fromthe method depicted in FIGS. 21A and 21B. The mesh 2120 has a closed endportion 2120 d and an open end portion 2120 e disposed at an angle tothe closed end portion 2120 d. The open end portion 2120 e can have asubstantially tubular configuration. In some embodiments, for example asshown in FIG. 21C, the closed end portion 2120 d encloses an open volumethat is substantially disc shaped with a protruding region formed by thefirst and second portions 2120 d 1, 2120 d 2 of the closed end portion2120 d of the mesh 2120. The protruding region may have a shape based onthe shape of the protrusion 2022 of the second member 2003. For example,the protruding region may be substantially cylindrical when formed overa cylindrical protrusion 2022. The first portion 2120 d 1 of the closedend portion 2120 d may be generally parallel to the third portion 2120 d3 of the closed end portion 2120 d of the mesh 2120. As shown in FIG.21C, the first portion 2120 d 1 may be offset from the third portion2120 d 3 by a length of the second portion 2120 d 2. The second portion2120 d 2 may be substantially perpendicular to the first and thirdportions 2120 d 1, 2120 d 3. Although the mesh 2120 shown in FIG. 21Cdepicts the first, second, and third portions 2120 d 1, 2120 d 2, 2120 d3 extending along substantially straight paths, in some embodiments thefirst portion 2120 d 1, the second portion 2120 d 2, and/or the thirdportion 2120 d 3 of the closed end portion 2120 d and/or the open endportion 2120 e extend along curved paths (see FIG. 21D). Moreover,although FIG. 21C depicts the first and third portions 2120 d 1, 2120 d3 disposed at an angle of about 90 degrees to the second portion 2120 d2 and the first portion 2120 d 1 disposed at an angle of about 90degrees of the closed end portion 2120 d of the mesh 2120, in someembodiments the above-noted angles may be different than 90 degrees.

CONCLUSION

Although many of the embodiments are described above with respect tomethods of manufacturing occlusive devices, the technology is applicableto other applications and/or other approaches. Moreover, otherembodiments in addition to those described herein are within the scopeof the technology. Additionally, several other embodiments of thetechnology can have different configurations, components, or proceduresthan those described herein. A person of ordinary skill in the art,therefore, will accordingly understand that the technology can haveother embodiments with additional elements, or the technology can haveother embodiments without several of the features shown and describedabove with reference to FIGS. 1A-21D.

As used herein, the terms “generally,” “substantially,” “about,” andsimilar terms are used as terms of approximation and not as terms ofdegree, and are intended to account for the inherent variations inmeasured or calculated values that would be recognized by those ofordinary skill in the art. The descriptions of embodiments of thetechnology are not intended to be exhaustive or to limit the technologyto the precise form disclosed above. Where the context permits, singularor plural terms may also include the plural or singular term,respectively. Although specific embodiments of, and examples for, thetechnology are described above for illustrative purposes, variousequivalent modifications are possible within the scope of thetechnology, as those skilled in the relevant art will recognize. Forexample, while steps are presented in a given order, alternativeembodiments may perform steps in a different order. The variousembodiments described herein may also be combined to provide furtherembodiments.

Moreover, unless the word “or” is expressly limited to mean only asingle item exclusive from the other items in reference to a list of twoor more items, then the use of “or” in such a list is to be interpretedas including (a) any single item in the list, (b) all of the items inthe list, or (c) any combination of the items in the list. Additionally,the term “comprising” is used throughout to mean including at least therecited feature(s) such that any greater number of the same featureand/or additional types of other features are not precluded. It willalso be appreciated that specific embodiments have been described hereinfor purposes of illustration, but that various modifications may be madewithout deviating from the technology. Further, while advantagesassociated with certain embodiments of the technology have beendescribed in the context of those embodiments, other embodiments mayalso exhibit such advantages, and not all embodiments need necessarilyexhibit such advantages to fall within the scope of the technology.Accordingly, the disclosure and associated technology can encompassother embodiments not expressly shown or described herein.

I/We claim:
 1. A method for making an occlusive device, the methodcomprising: obtaining a tubular mesh having a lumen therethrough;obtaining a forming member having an outer surface and an inner surface;everting the mesh over the forming member such that a first portion ofthe mesh conforms to the outer surface of the forming member and asecond portion of the mesh conforms to the inner surface of the formingmember; setting a shape of the mesh while positioned over the formingmember.
 2. The method of claim 1, wherein the forming member is a firstforming member, the inner surface is a first mating surface, and themethod further comprises positioning the second portion of the meshbetween the first mating surface of the first forming member and asecond mating surface of a second forming member such that the secondportion of the mesh conforms to the first and second mating surfaces ofthe first and second forming members, respectively.
 3. The method ofclaim 2, further comprising compressing the second portion of the meshbetween the first and second mating surfaces.
 4. The method of claim 1,further comprising positioning an elongate member within the lumen ofthe mesh and conforming a third portion of the mesh to the elongatemember.
 5. The method of claim 1, wherein setting the shape of the meshcomprises heat-treating the mesh while positioned on the forming member.6. The method of claim 1, wherein, when positioned over the formingmember, the first portion of the mesh is spaced apart from the secondportion of the mesh by a thickness of the forming member between theinner and outer surfaces.
 7. The method of claim 1, wherein, aftersetting the shape of the mesh, the first and second portions of the meshform a dual-layer sidewall that encloses an open volume.
 8. The methodof claim 1, wherein the forming member includes a lumen extendingtherethrough.
 9. The method of claim 1, wherein the inner surface of theforming member is arcuate and defines a cavity in the forming member.10. A method for making an occlusive device, the method comprising:obtaining a tubular mesh having a lumen extending therethrough and aporosity configured to substantially prevent blood flow through themesh, the mesh comprising first and second end portions and anintermediate portion therebetween; obtaining a forming assemblycomprising: a first member having a generally globular shape and a lumenextending therethrough, wherein the first member has a first matingsurface comprising at least a portion of an outer surface of the firstmember; and a second member having a generally hemispherical shape and acavity with an arcuate surface, the second member having a lumenextending therethrough; positioning at least a first portion of theintermediate portion of the mesh over an outer surface of the secondmember; positioning at least a portion of the first end portion of themesh within the lumen of the first member; positioning at least a secondportion of the intermediate portion of the mesh between the first matingsurface of the first member and the arcuate surface of the second membersuch that the second portion substantially conforms to the first matingsurface and the arcuate surface; setting a shape of the mesh while themesh is positioned on the forming assembly.
 11. The method of claim 9,wherein positioning the second portion of the intermediate portion ofthe mesh between the first mating surface of the first member and thearcuate surface of the second member comprises positioning the firstmember at least partially within the cavity of the second member. 12.The method of claim 9, wherein, after setting the shape of the mesh, themesh comprises a contoured configuration in which the first and secondend portions of the mesh have a substantially tubular shape and theintermediate portion of the mesh is substantially bowl-shaped.
 13. Themethod of claim 9, further comprising positioning an elongate memberwithin the lumen of the tubular mesh, the lumen of the second member,and the lumen of the second member and conforming the first and secondend portions of the mesh to an outer surface of the elongate member. 14.The method of claim 9, further comprising coupling a first couplingelement to the second end portion of the mesh at a location adjacent anouter surface of the second member and coupling a second couplingelement to the first end portion of the mesh at a location adjacent thearcuate surface of the second member.
 15. A method for making anocclusive device, the method comprising: obtaining a tubular mesh havinga lumen extending therethrough and a porosity configured tosubstantially prevent blood flow through the mesh, the mesh comprisingfirst and second end portions and an intermediate portion therebetween;obtaining a forming member having a first surface, a second surfaceopposite the first surface along a thickness of the forming member, asidewall therebetween, and a lumen extending through the first andsecond surfaces of the forming member; positioning at least a firstportion of the intermediate portion of the mesh within the lumen of theforming member such that the first end portion of the mesh extends awayfrom the first surface of the forming member in a first direction andthe second end portion of the mesh extends away from the second surfaceof the forming member in a second direction opposite the firstdirection; everting the mesh over the forming member such that the firstand second end portions of the mesh extend away from the second surfaceof the forming member in the second direction, wherein everting the meshcauses the first end portion of the mesh to substantially conform to thefirst and second surfaces and the sidewall of the forming member; andsetting a shape of the mesh while positioned on the forming member. 16.The method of claim 14, further comprising positioning an elongatemember within the lumen of the tubular mesh and the lumen of the formingmember and further comprising conforming the first and second endportions of the mesh to an outer surface of the elongate member.
 17. Themethod of claim 14, wherein the sidewall is annular such that theforming member comprises a generally cylindrical shape.
 18. The methodof claim 14, wherein, after setting a shape of the mesh, the meshcomprises a contoured configuration comprising a substantially tubularopen end portion, a substantially tubular intermediate portion, and asubstantially disc shaped closed end portion disposed at an angle to theopen end and intermediate portions.
 19. The method of claim 14, whereinthe forming member is a first forming member and, after setting theshape of the mesh, the mesh is a contoured mesh, the method furthercomprising: separating the contoured mesh from the first forming member;obtaining a forming assembly comprising a second forming member and athird forming member, wherein: the second forming member comprises abody portion having a first surface, a second surface opposite the firstsurface along a thickness of the second forming member, a sidewalltherebetween, a protrusion extending from the first surface in a firstdirection, and a lumen extending through the body portion and theprotrusion; and the third forming member comprises a body portion havinga first surface, a second surface opposite the first surface along athickness of the third forming member, a sidewall therebetween, and alumen extending through the body portion; positioning the intermediateportion of the contoured mesh within the lumen of the second formingmember such that the closed end portion of the contoured mesh extendsfrom the first surface of the second forming member and the open endportion of the contoured mesh extends from the second surface of thesecond forming member; positioning the closed end portion of thecontoured mesh between the first surface and the protrusion of thesecond forming member and the second surface of the third forming membersuch that the closed end portion of the contoured mesh conforms to thefirst surface and the protrusion of the second forming member; andsetting a second shape of the contoured mesh based on the second andthird forming members.
 20. The method of claim 18, wherein, aftersetting a second shape of the contoured mesh, the contoured meshcomprises a substantially tubular open end portion, a substantiallytubular intermediate portion, and a closed end portion disposed at anangle to the open end and intermediate portions, wherein the closed endportion is substantially disc shaped with a protruding region.